Developmental, Physiologic and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles

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Developmental, Physiologic and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles

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Joseph Foon Yoong Hoh^*

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Submitted:

09 March 2024

Posted:

11 March 2024

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Abstract

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

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Subject: Biology and Life Sciences - Anatomy and Physiology

1. Craniofacial Muscles and Their Developmental Origins

Muscles that move different parts of the body are associated with unique properties that equip them to meet different types of functional demands made upon them. The main functions of limb and trunk muscles are locomotion and the maintenance of posture which are well served by 4 types of muscle fibres, the β-slow and 3 subtypes of fast fibres, 2a, 2x and 2b. The functional demands on craniofacial muscles are much more varied and complex. Among other functions, they must cope with the complex movements of the eyes, move the jaw in different animals in diverse modes of predation and feeding, regulate respiration and protect the airway. To meet these functional demands, a wider range of muscle fibre types which include those with contractile properties faster and slower than those in limb muscles is needed. The origin of these differences in fibre type composition between craniofacial and limb muscles can be traced to the diversity of the premyogenic mesodermal cell lineages that give rise to them.

Myogenic cells forming muscles in different regions of the body arise from myogenic progenitor cells of the paraxial mesoderm of the early embryo. These progenitor cells are committed to different lineages of myogenic cells by diverse regulatory factors [1]. Limb and trunk muscles develop from cells in the segmented somites on each side of the developing spinal cord. Extraocular muscles (EOMs) develop from cells that originate from the prechordal plate [2,3] and the first branchial arch [4]. Other craniofacial muscles originate from progenitor myoblasts in the unsegmented cranial paraxial mesoderm and from the most rostral occipital somites [5]. These progenitor myoblasts migrate into the branchial arches. Jaw muscle cells are derived from the first branchial arch, the intrinsic laryngeal muscles from the fourth arch and the sixth arch [6]. Expression of the pituitary homeobox gene 2 (Pitx2) commits progenitor myoblasts from the prechordal plate to the EOM myoblast lineage, while expression of Pitx2 and T-box gene 1 (Tbx1) commits progenitor myoblasts to the branchial myoblast lineage, in contrast to the expression of Pitx3 gene which commits somitic progenitors to trunk and limb myoblast lineage [1,7]. Progenitor myoblasts in the branchial arches and somites are further specified by different transcription factors into various myogenic lineages and ultimately bring about myogenesis by the four myogenic regulatory factors: Myf5, Mrf4, MyoD and myogenin. Myf5, Mrf4 and MyoD commit progenitor myoblasts to the myogenic fate, while myogenin, the terminal differentiation factor, initiates the differentiation of myoblasts into muscle fibres [8,9].

2. Myosin Heavy Chain and Light Chain Isoforms and Their Genes

Myosin controls the kinetics of chemo-mechanical energy transduction from ATP in muscle, and thus the kinetic properties of muscle fibres. The speed of contraction of a muscle is generally proportional to the ATPase activity of its myosin [10]. As the maximal stress of muscles of different speeds is about the same, muscle power (force x velocity) is also a function of myosin ATPase activity. Thus, the myosin isoform expressed in a muscle fibre determines its speed and power and serves as the primary basis for fibre type classification.

Myosin is a hexamer consisting of a pair of heavy chains (MyHC) and two pairs of light chains (MLCs) which together form a two-headed molecule with an elongated rod-like tail. The C-terminal halves of the MyHCs are α-helical and wrap around each other to form the tail, while the N-terminal halves form the globular heads, each of which contains an ATPase site and an actin binding site. Each head is attached to the rod by an α-helical lever arm to which the essential light chain (MLC1) and the regulatory light chain (MLC2) are attached. In striated muscles, myosin molecules assemble into thick filaments by the antiparallel packing of the rod portion of myosin molecules forming bipolar structures with a central bare zone, on either side of which the myosin heads are helically arranged on the filament surface. During muscle contraction, myosin heads act as cross-bridges between thick and thin filaments that cyclically interact with actin molecules of the thin filaments, hydrolysing ATP and generating force and movement between filaments. During the chemo-mechanical coupling, the small conformational change in the catalytic domain of the head gets amplified by the lever arm [11]. This cyclic activity generates the relative force and motion between the thick and thin filaments which underlie the sliding filament theory of muscle contraction [12].

Twelve MyHC genes are known to be expressed in mammalian striated muscles, namely, the eleven striated muscle MyHC genes [13] and the non-muscle MyHC IIB (nmMyH IIB) gene (MYH10) which is only expressed in sarcomeres of extraocular muscle [14]. The eleven striated muscle MyHC genes include the six skeletal MyHCs which are clustered in tandem in the mammalian genome [15] in the following order: embryonic (MYH3), fast 2A (MYH2), 2X (MYH1), 2B (MYH4), neonatal (MYH8) and extraocular (EO) (MYH13). There are two cardiac MyHC genes, α-cardiac (MYH6) and β-cardiac, the latter is identical to that of slow skeletal MyHC gene and is designated as β-slow (MYH7). The α-cardiac and β-slow genes are also arranged in tandem in the genome [16,17]. There are two EOM-specific MyHC genes, the slow-tonic (MYH14/7b), slow B (MYH15) [18,19], and finally a highly jaw-specific and most ancient masticatory MyHC gene (MYH16) [20]. The expression of different MyHCs with their various associated isoforms of MLC1 and MLC2 in different fibres generates muscle fibre types with a wide range of kinetic characteristics to meet the diverse functional demands on craniofacial muscles.

Myosin light chains are classified into those associated with fast muscle fibres (MLC1_F, MLC2_F and MLC3_F), slow skeletal fibres/ventricular myocardium (MLC1_S, MLC2_S), atrial myocardium (MLC1_A, MLC2_A) and masticatory fibres (MLC1_M, MLC2_M). The essential light chain of fast myosins exits as two isoforms (MLC1_F and MLC3_F) [21] which are spliced variants of the MLC1_F/MLC3_F gene (MYL1) [22]. These isoforms share a C-terminal sequence, but differ in the N-terminal region, MLC1_F having 38 amino acid residues more than MLC3_F.

The functional significance of fast MLC1 heterogeneity is the modulation of cross-bridge kinetics of fast myosins. Fast myosin with MLC3_F moves actin filaments faster in motility assays than fast myosin with MLC1_F [23]. The maximal velocity of shortening (Vmax) of rabbit fast fibres is proportional to the content of MLC3_F [24]. The MLC1_F isoform with the larger N-terminal domain has a greater affinity for actin [25], thereby retarding cross-bridge detachment rate during the cross-bridge cycle.

The MLC1 of embryonic (MLC1_E) [26], atrial (MLC1_A) [27] and masticatory (MLC1_M) [28] myosins were initially thought to be distinct entities. However, later work revealed that MLC1_E and MLC1_A are identical [22,29] and have been designated as MLC1_E/A, and that MLC1_M is identical to MLC1_E/A [30]. MLC1_E/A and MLC1_S are encoded by MYL4 and MYL3 respectively [31]. The N-terminal of MLC1_E/A has fewer charged amino acid residues compared with slow/ventricular MLC1_S and has a weaker interaction with actin [32]. The β-slow MyHC may be associated with either MLC1_E/A or MLC1_S. The cross-bridge cycling rate of β-slow myosin associated with MLC1_E/A in cat jaw-slow fibres (see later) is considerably higher than that associated with MLC1_S in β-slow limb fibres [33].

The regulatory light chain MLC2 in striated muscles exists as four isoforms, each encoded by a distinct gene [34]: the fast skeletal isoform MLC2_F encoded by MYL2_F [35], the ventricular/slow skeletal isoform MLC_S (MYL2) [36,37], the atrial isoform MLC2_A (MYL2_A) [38] and embryonic/masticatory isoform MLC2_M (MYL5) [39,40].

The functional significance of MLC2 lies in the fact that its helps to stabilize the myosin interacting head motive (IHM, see later), the destabilization of which by MLC2_F phosphorylation is the basis of post-tetanic twitch potentiation in which thick filament-bound cross-bridges swing out towards thin filaments leading to enhance contractility (see later). The structure of MLC2_M may have a similar destabilizing effect on IHM as phosphorylated MLC2_F which may possibly explain the preponderance of protruding cross-bridges in masticatory fibres [41].

3. Kinetic Properties of Myosin Isoforms

Mechanical analyses on EOM [42,43,44] and single EOM fibres [45,46] have established that EO myosin is the fastest isoform. Of the isoforms found in limb and trunk muscles, 2B, 2X, 2A and β-slow myosins are in descending order of speed [47,48,49]. The α-cardiac myosin is two to three-fold faster than β-slow myosin containing the same MLCs [50,51], placing the kinetic properties of α-cardiac myosin close to that of 2A myosin. This is consistent with the Vmax of rabbit skeletal muscle fibres containing α-cardiac myosin, which lies between the Vmax of fibres expressing β-slow and 2A myosin [52]. The kinetics of β-slow myosin is more sensitive to temperature than that of α-cardiac myosin [50,53] and limb fast myosins [1,33,45]. This implies that β-slow myosin has a higher activation energy, reflecting a more stable attached cross-bridge, an increased time that β-slow myosin is bound to actin and a slower ADP dissociation rate from actin-myosin complex [54]. These characteristics underlie the low tension-cost of β-slow skeletal fibres [55] and hearts [56] expressing the same β-slow myosin.

The velocities of shortening of new-born fast and slow rat limb muscles are virtually the same as that of adult slow muscle [57]. Since these muscles express predominantly neonatal myosin [21,58,59], Vmax of fibres with neonatal myosin is thus close to that of β-slow myosin. However, model analysis of human neonatal myosin suggest that it shares some kinetic characteristics with fast myosins [60]. Slow B myosin, an orthologue of amphibian ventricular MyHC, is uniquely expressed in orbital fibres of rat EOMs [18]. The kinetics of embryonic and slow B myosins have not been specifically determined but are likely to be as slow or slower than β-slow myosin [61]. The very slow contractions of multiply-innervated EOM fibres of the rabbit [62] and cat [63,64,65] can be attributed to the presence of slow-tonic myosin. This myosin is closely related to the myosin in slow-tonic fibres in birds and amphibians [66,67], which produce very slow contractures [68,69]. Recent kinetic analysis of recombinent human slow-tonic myosin revealed that its maximal actin activated ATPase activity is half that of human β-slow myosin and that a high proportion of the slow-tonic myosin heads are in the super-relaxed (SRX) state with very low ATPase activity [70].

4. Modulation of Contractility by Thick Filament Proteins

While contractile properties of muscle fibres are primarily determined by the myosin isoform, molecular interactions of myosin with itself and with other components of the thick filament, titin and myosin binding protein-C (MyBP-C), also play a role. On either side of the thick filament bare zone, most myosin heads are bound to the core of the thick filament, forming an ordered helical array, the two heads of each myosin molecule interact with each other and are folded back against the thick filament, forming a stable IHM. Titin extends from the Z-disc to the M-line in the centre of the bare zone, interacting with the thick filament along the way in each half sarcomere, while MyBP-C is located in the central third of each half sarcomere called the C-zone. Myosin heads forming the IHM are in a SRX state with very low Mg-ATPase activity [71] and are in the OFF state, being not competent to interact with activated thin filaments. However, a proportion of myosin heads in resting muscle are not attached to the thick filament but are swung out towards the thin filament in a disordered relaxed (DRX) state with much higher Mg-ATPase activity relative to the SRX state. These cross-bridges are in the ON state and are competent to bind activated actin filaments. Upon thin filament activation by Ca²⁺, these ON cross-bridges bind actin, produce tension, inducing stress along the thick filament. Thick filament stress destabilizes OFF cross-bridges into the ON state and interact with actin, generating more tension in a positive feedback process termed mechano-sensing [72,73,74,75]. Mechanisms that disrupt the IHM would also increase the population of ON cross-bridges and generate more stress on the thick filament, thereby modulate the contractile properties of muscle fibres through mechano-sensing. This occurs during post-tetanic potentiation in fast fibres in which MLC2_F is phosphorylated during a tetanus by Ca²⁺-calmodulin activated myosin light chain kinase [76,77]. X-ray diffraction analysis revealed that after phosphorylation of MLC2_F, more myosin heads are shifted away from thick filaments towards thin filaments [78].

MyBP-C can also influence contraction by modulating the IHM. There are 4 fibre type specific MyBP-C isoforms: fast (fMyBP-C), slow (sMyBP-C), cardiac (cMyBP-C) [79] and masticatory (mMyBP-C) [80,81], the existence of mMyBP-C has largely been ignored in the field. Fast muscle fibres express both fMyBP-C and sMyBP-C in roughly equal proportions whiles slow muscle fibres express virtually only sMyBP-C [82], and mMyBP-C is expressed specifically in masticatory fibres of jaw-closing muscles. MyBP-C is an elongated, flexible polypeptide made up of a series of globular immunoglobulin (Ig)-like domains and fibronectin type 3 (Fn3) domains. The sMyBP-C and fMyBP-C both contain 10 Ig/Fn3 domains, with a fibre-type specific MyBP-C motif inserted between the first and second Ig domains in the N-terminal region. The C-terminal region of MyBP-C is tightly bound to the thick filament by interacting with myosin rods and with titin. cMyBP-C and sMyBP-C have phosphorylation sites in their N-terminals. These N-terminals can bind either thick or thin filament depending on their phosphorylation status. In cardiac muscle, the N-terminals of unphosphorylated cMyBP-C stabilize the OFF state of cross-bridges. Phosphorylation of cMyBP-C by cAMP-activated protein kinase, which occurs following β-adrenergic stimulation, destabilizes the IHM, enhancing the number of ON cross-bridges and thus cardiac contractility [83], accounting largely for the inotropic response to β-adrenergic stimulation [84].

Less is known about the roles of sMyBP-C and fMyBP-C in modulating skeletal muscle contractility. Analysis of ATPase activity using single-molecule fluorescence imaging techniques along the thick filament in β-slow skeletal muscle sarcomeres suggests that sMyBP-C does influence the distribution of SRX and DRX cross-bridges [85]. Mechanical analysis of transient force overshoot in slow muscle using a relax and re-stretch protocol suggests a model in which it is the unphosphorylated N-terminals of sMyBP-C which bind to thin filaments, forming links between filaments which retard filament sliding. Phosphorylation of N-terminals of sMyBP-C by cAMP-activated protein kinase detaches them from thin filaments and bind to thick filaments. This releases the links between thick and thin filaments, thereby facilitating filament sliding. The binding of phosphorylated N-terminals to thick filaments leads to enhanced rate and magnitude of force development presumably by turning OFF cross-bridges into the ON state [86].

Relatively little is currently known about the role of MyBP-C in the modulation of craniofacial muscle contraction. All EOM fibres have been reported to express sMyBP-C [87]. A jaw-specific mMyBP-C is expressed in masticatory fibres of carnivores [80,81] and a single unidentified MyBP-C isoform which has an electrophoretic mobility similar to that of sMyBP-C is found in human masseter muscle [88]. MyBP-C expression in laryngeal muscles has yet to be investigated.

5. MyHC Expression Repertoire of Craniofacial Muscles

Across mammalian species, the specific MyHC isoforms expressed in the muscle fibres of a given animal are matched to the functional requirements of the structure the muscle fibres move. Craniofacial muscles have very different repertoires for MyHC gene expression compared to muscles of somitic origin. The repertoire of limb and truck muscles comprise β-slow, 2A, 2X and 2B MyHCs expressed in β-slow, 2a, 2x and 2b fibres respectively. Adult EOMs express nmMyH IIB MyHC and all striated muscle MyHC isoforms except the masticatory MyHC [89]. This means that EOMs express 11 kinetically distinct MyHC isoforms. The extremely wide range of kinetic properties of these MyHC isoforms together with their complex distribution in various fibre types and variations along fibre lengths enable EOMs to execute very fast saccades without overshoot, ripple-free eye fixation, as well as various other types of eye movements.

MyHC isoforms expressed in jaw-closer muscles of different mammalian taxa vary widely to match the masticatory requirements of the wide range of diets and feeding habits [90]. These include the high force and highly jaw-specific masticatory MyHC in carnivores and other animals, α-cardiac and β-slow MyHCs in herbivore and limb MyHCs in omnivores.

Laryngeal muscles express limb muscle MyHC isoforms, with the profile of MyHCs shifting towards faster isoforms in smaller animals, the smallest animals also express the superfast EO MyHC. This pattern of MyHC expression enables laryngeal muscles of animal of varying body mass to cope with respiratory rate changes associated with increasing basal metabolic rate with decreasing body mass [91].

6. Craniofacial Muscle Allotypes

The capacity of craniofacial muscles to express different isoforms of MyHC and other myofibrillar proteins are intrinsic to the lineage of myoblasts which give rise to them. Cat temporalis muscle regenerated from temporalis muscle satellite cells and innervated by limb fast muscle nerve express masticatory MyHC [92] and the jaw-specific mMyBP-C and tropomyosin (m-Tm) [93] rather than limb muscle isoforms of these proteins. Even uninnervated temporalis regenerates express masticatory MyHC [94] and myotubes derived from tissue cultures of satellite cells from cat temporalis muscle express masticatory MyHC, mMyBP-C and m-Tm [81]. Further, transplanted cat temporalis muscle innervated by limb slow muscle nerve express not limb β-slow myosin but an immunochemically distinct jaw-specific β-slow myosin [92,93] with β-slow MyHCs associated with masticatory MLC1_M, MLC2_M [33,95]. These results indicate that the capacity to express masticatory myosin, mMyBP-C, m-Tm and jaw-specific slow myosin is intrinsic to the temporalis myoblast lineage. The term allotype has been used to classify muscles from different body regions with different repertoires for expressing myosins and other myofibrillar proteins.

The status of EOM as a distinct allotype has also been examined. Initial experiments on myotubes in cultured mouse EOM satellite cell and on mouse limb fast muscle with incorporated EOM satellite cells failed to express EO and slow-tonic MyHCs specific to EOMs [1]. Regenerated rabbit EOM innervated by limb fast muscle nerve also do not express EO MyHC. However, EOM regenerates innervated by the oculomotor nerve do express EO MyHC [89], confirming that myogenic cells of EOM can express the EOM-specific MyHC, and that EOM is also a distinct allotype. The failure of EOM regenerates innervated by limb muscle nerve to express EO MyHC may be due to the absence of a neural impulse pattern necessary for its expression. The oculomotor nerve can deliver very high frequency impulses [96] especially during saccades [97,98]. High frequency impulses may be necessary for inducing EO MyHC expression but are absent from limb muscle nerves. It remains for future research to confirm that very high frequency impulses per se are specifically required for inducing EO MyHC expression in regenerating EOMs. Consistent with EOM being a distinct allotype, these muscles show different susceptibilities to muscle disease compared to limb muscles, being spared in Duchenne muscular dystrophy [99] but are early and prominent targets in myasthenia gravis [100].

Several observations suggest that laryngeal muscles are also allotypically distinct from other craniofacial and limb muscles. The capacity of rat thyroarytenoid muscle to express EO MyHC but not β-slow and 2A MyHCs is unaffected by cross-innervation by the nerve to the sternohyoid, a somitic muscle which expresses limb MyHCs but not EO MyHC [101]. Although the cricothyroid (CT) in most mammals expresses limb muscle myosin isoforms [102], it is highly specialized in bats for producing ultrasonic sound pulses for echolocation. Bat CT is an extremely fast muscle [103] in which the sarcoplasmic reticulum volume occupying 30% of the fibre volume [104] and the mitochondrial density is enhanced [105]. The CT and other laryngeal muscles are also differentially susceptible to disease. Videolaryngoscopic examination of laryngeal muscle function in patients with Duchenne muscular dystrophy suggests that vocal fold adductors and abductors are spared in this disease [106]. In a mouse model of this disease, the CT is affected while the other laryngeal muscles are spared [107,108,109], reflecting a difference in allotype between the CT and other laryngeal muscles.

This review will examine the developmental origins of the major craniofacial muscles, the expression, regulation and functional significance of MyHCs they express and changes in MyHC expression during phylogeny. It will focus on how differences in MyHC expression meet the diverse functional demands of the various organs they move and how changes in their functional demands during phylogeny are met by changes in MyHC expression. Table 1 lists the MyHC expression repertoires of extraocular, masticatory and laryngeal muscle allotypes.

7. Developmental Origin of EOMs

EOMs develop from two components of head mesoderm, the first component arise from paraxial mesoderm related to the first branchial arch, giving rise to the lateral rectus and superior oblique muscles. The other portion is of prechordal mesodermal origin and gives rise to the other four EOMs (medial rectus, inferior rectus, superior rectus, and inferior oblique) [2,4,110]. Normal development of the EOMs requires input signals from both the developing eye and surrounding cranial neural crest cells [4]. Expression of Pitx2 gene is necessary for the specification of EOM myoblasts [111], in contrast to the corresponding requirement of Pax3 for somitic myoblasts [112]. Pitx2 activates myf5, myf6 and MyoD1 to commit premyogenic cells to EOM myogenesis [1,113], while myogenin initiates EOM myogenesis. Postnatal knockout of Pitx2 gene shows that the continued expression of Pitx2 in adult EOM fibres is necessary for the maintenance of EOM-specific characteristics such as polyneuronal innervation and slow-tonic MyHC expression [114,115].

8. Ontogeny of EOMs

Changes in MyHC expression in EOM during perinatal development in the rat [116,117] and following postnatal experimental manipulations [118,119] have been reported. Early during EOM myogenesis, primary and secondary myotubes emerge in succession from primary and secondary myoblasts just as in developing muscles elsewhere. At E16 (embryonic day 16) only primary myotubes are seen, expressing β-slow MyHC strongly and embryonic/neonatal MyHCs weakly. Secondary myotubes appear at E17, expressing embryonic/neonatal MyHCs but not β-slow MyHC. Thus far, the pattern of MyHC expression in these myotubes resemble those in limb muscles. Subsequently, the division of EOMs into orbital and global layers begins to emerge. Some orbital but not global primary myotubes begin to express slow-tonic MyHC at E19 [116]. In rats at birth, β-slow MyHC is exclusively localized to primary fibres, embryonic/neonatal MyHCs are present in all fibres, while fast MyHCs are expressed only in secondary fibres [117]. In postnatal mice, β-slow MyHC is exclusively localized to evenly distributed small fibres presumably of primary myotube origin while fast MyHCs are expressed in larger surrounding fibres presumably of secondary myotube origin [120]. In adult rabbit EOM, β-slow MyHC is also exclusively localized to multiply-innervated fibres (MIFs) and fast MyHCs exclusively localized in singly-innervated fibres (SIFs). These results suggest that primary myotubes become MIFs while secondary myotubes become SIFs.

During the first 2-3 weeks of postnatal life in the rat, dramatic changes in MyHC expression occur: neonatal and embryonic MyHCs are downregulated in the global fibres but are retained in the orbital fibres [117], and 2A/2X [116], EO [121], nmMyH IIB [122] and slow B [18] MyHCs progressively emerge. These changes are associated with progressive maturation of oculomotor neurons and the visual nervous system, and eye opening at around 2 weeks postnatally. During this period the ratio of tonic to phasic discharge patterns of motoneurons increases about tenfold and the maximal frequency of discharge of oculomotor neurons rises from 150 to 420 Hz [96]. Postnatal dark rearing decreases the proportion of fibres expressing β-slow and fast MyHCs and reduces the expression of EO MyHC mRNA [118], while chemical destruction of vestibular hair cells postnatally increases the proportion of developmental and fast MyHCs and decreases EO MyHC mRNA expression [119]. These results strongly suggest that postnatal changes in oculomotor impulse pattern via inputs from visual and vestibular pathways induce the expression of various MyHCs that emerge postnatally.

In mice with postnatal knockout of Pitx2, the expression of β-slow and slow-tonic MyHCs, along with troponin I and troponin T, is reduced during the first 3 weeks after birth. This is associated with the loss of en grappe neuromuscular junctions and polyneuronal innervation, suggesting that the expression of β-slow and slow-tonic MyHCs is regulated by the tonic motoneurons normally innervating MIFs [115].

Our current understanding of EOM development is woefully incomplete. For example, we do not know the cellular and molecular basis of the division of EOMs into global and orbital layers, nor the basis for the variation of MyHC expression along the fibre length. In limb muscles, the postnatal surge of thyroid hormone [123] and emergence of different neural impulse patterns play key roles in muscle fibre maturation [124]. While the role of the nerve is proposed below, there has apparently been no study of the possible role of thyroid hormone in postnatal MyHC expression in EOMs.

9. Neural Regulation of MyHC Expression during EOM Myogenesis: An Hypothesis

The integrity and synaptic connectivity of different types of ocular motoneurons are sustained by different retrogradely transported muscle-derived neurotrophins [125] which specify their synaptic inputs and thus the efferent neural impulse patterns (see later). Oculomotor neurons depend on these trophic factors for their survival during development [126]. Neonatal EOMs richly express these neurotrophic factors, and exogenous replacement of these factors significantly rescued extraocular motoneurons from axotomy-induced cell death [127]. Myogenic cells isolated from EOMs also express high levels of neurotrophins [128]. It is thus likely that synaptic inputs of slow-tonic and phasic motoneurons innervating MIFs and SIFs, respectively, are modulated during development by different target-derived neurotrophins from contact with primary and secondary myotubes, respectively. In other words, through the different neurotrophic factors retrogradely transported to their motoneurons, primary and secondary myotubes may choreograph the tonic and phasic types of neuronal impulse pattern they respectively receive. These patterns would, according to the impulse pattern hypothesis (see below), control MyHC expression in a frequency dependent manner during postnatal development as well as the maintenance of the MyHC expression pattern during adult life.

10. Functional Demands on EOMs

The functional demands on EOMs are highly complex but are very similar across the species, in sharp contrast to widely varied demands on jaw-closing muscles. The nervous system has evolved mechanisms to control the EOMs to move the two eyes as a functional unit to optimize vision [129,130]. To obtain good vision, both eyes must fixate on the same object of interest. If the head moves, the eyes must make precise compensatory movements in the opposite direction to maintain visual acuity. The vestibulo-ocular system and the optokinetic system must compensate for large and small head motion by producing perfectly matched counter rotations of the eyes. There are two gaze-shifting mechanisms: (1) saccadic system, which rapidly shifts gaze from one point to another, and (2) smooth pursuit system, which allows the eyes to track a moving target. To keeps both eyes aligned with visual targets at various distances from the eyes, there is the vergence system, which is better developed in front-eyed animals and predators than lateral-eyed animals and preys. These neural systems converge on ocular motoneurons which control the six EOMs [131], each of which containing six different fibre types [132] to cater for the functional demands on EOMs. Functional demands are greatest during a saccade in which the eyes rapidly and accurately move from one fixation point to another in an almost linear fashion without overshoot. Eye movements must also satisfy Listing’s law which governs the axis of rotation of the eye in three-dimensional space [133].

11. EOM Fibre Types

To meet the very complex functional demands, EOM fibres are highly specialized and differ substantially from other craniofacial and limb muscle fibres in many characteristics, including innervation, fibre types, MyHC composition and gene expression profile [132]. They have MIFs resembling slow-tonic fibres in amphibians and express unique MyHCs [18,134]. Single EOM fibres co-express multiple MyHC isoforms which may vary along the fibre length [135,136,137,138,139]. The pattern of gene expression in EOMs differs from that limb muscles and have been documented by proteomics [140] and mRNA profiling [140,141,142,143].

The fibres of EOMs are organized into two layers, a thin orbital layer facing the orbit and a thicker global layer facing the globe [144,145]. Both layers are made up of (1) SIFs with large en plaque nerve endings, and (2) MIFs with small en grappe endings. Using ultrastructural and histochemical criteria, fibres in the orbital (o) and global (g) layers can be classified into 6 fibre types: oSIF and oMIF in the orbital layer and gSIF-red, gSIF-intermediate, gSIF-white and gMIF in the global layer [132].

The oSIF have small myofibrils, well developed T-tubules and moderately developed sarcoplasmic reticulum, rich in mitochondria and oxidative enzymes, suggesting that they are fatigue resistant. The three types of gSIFs vary in fibre diameter, the SIF-red fibres are small, rich in mitochondria and oxidative enzymes, suggesting high fatigue resistance, gSIF-white are large, poor in mitochondria but rich in glycolytic enzymes, suggesting high fatigability, while oSIF-intermediate fibres have intermediate values for these characteristics [132].

MIFs generally have large myofibrils, few mitochondria, poorly developed T-tubules and sarcoplasmic reticulum. While oMIFs receive an extra en plaque endplate in the middle of the fibre and can generate non-overshooting action potential in this local region [146] and thus can produce twitch responses [146,147], gMIFs cannot initiate an action potential, resembling the non-twitch, slow-tonic fibres found in amphibian limb muscles [68,69].

The gMIFs in some animals have innervated structures called palisade endings or innervated myotendinous cylinders [148] at their myotendinous junctions. Palisade endings resemble immature Golgi tendon organs and are found in all front-eyed mammals studied but absent in some lateral-eyed mammals [149]. They are innervated by axon extensions of nerve fibres of oculomotor neurons innervating gMIFs [150,151]. The function of palisade endings is highly controversial, many workers regarding them as proprioceptive receptors [152], but others believe that they are motor in nature [153,154]. It has been hypothesized that palisade endings in front-eyed animals are mechano-receptors that can be activated by gMIF contraction as well as by passive stretch to generate axon reflexes that activate gMIF motor units to enhance their force output during fixation, saccades and vergence [89]. Since gMIFs are multiply innervated, the gMIF/palisade ending complex acts like a motoneuron with afferent synaptic inputs from several gMIF motoneurons, integrating not their endplate potentials, but summing their tension contributions to stimulate the palisade ending to generate neural impulses to produce tension from the gMIF motor unit of which it is a part.

The pattern of gene expression in orbital and global layers differ [155,156]. Fibres of the orbital layer are short and insert onto connective tissue pulleys attached to the orbital wall [157], though some orbital fibres do insert onto the eyeball [139,158] and some global fibres in human and monkey EOMs also insert onto their pulleys [159]. Orbital fibres have long been implicated in fixation [160,161,162], but many workers currently hold that orbital fibres move the pulleys which modulate the direction of rotation of the eyeball to implement Listing’s law [163,164] and that only global fibres move the eyeball. Little is currently known about the cellular and molecular bases for the division of EOMs into orbital and global layers.

12. Ocular Motoneurons Innervating MIFs and SIFs

Motoneurons supplying SIFs and MIFs are located in different regions of the ocular motor nuclei. Motoneurons innervating SIFs are located within the classical ocular motor nuclei, whereas those innervating MIFs are located in the periphery of these nuclei [165]. Two populations of neurons have been identified in this peripheral region in the monkey oculomotor nucleus [166], a population of small, multipolar neurons innervate palisade endings and their gMIFs [167,168], while the other population of round or spindle-shaped cells probably innervate oMIFs.

The firing pattern of ocular motoneurons span a wide spectrum ranging from tonic to phasic [169]. SIF motoneurons have high thresholds, high velocity sensitivities, are deployed infrequently, and deliver a range of high-frequency bursts during saccades. MIF motoneurons participate in all types of eye movements as SIF motoneurons but are recruited earlier and show lower eye position and eye velocity sensitivities than SIF motoneurons, and fire at relatively low frequencies [98].

Neurotrophins play important roles during neuronal development and in adult life, when they act as mediators of synaptic and morphological plasticity [170,171]. The integrity and synaptic connectivity of ocular motoneurons are sustained by different muscle-derived neurotrophins, as in the case of spinal and other craniofacial motoneurons [125]. The burst and step features of ocular motoneuron impulses are generated by different synaptic inputs and are maintained by different neurotrophins retrogradely transported from muscle fibres they innervate [125]. Muscle fibres [172], including EOM fibres [127] abundantly express brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF). Following axotomy, ocular motoneurons lose most of their synapses, resulting in reduced impulse frequency and reduced position and velocity sensitivities [170]. The administration of neurotrophins to the proximal nerve stump restores the afferent synaptic contacts and firing characteristics of axotomized ocular motoneurons, BDNF restores tonic firing, NT-3 restores saccadic bursts [170] while NGF has an influence on both types of activity [173]. Since myogenic cells isolated from EOMs express high levels of neurotrophins [128], these interactions between muscle and nerve would presumably occur following the initial innervation of primary and secondary myotubes by MIF and SIF motoneurons respectively, resulting in their different neural impulse patterns that regulate the postnatal changes in MyHC expression in MIFs and SIFs.

13. Longitudinal Variations in EOM Fibre Characteristics and Their Functional Significance

An outstanding feature of the oSIFs and oMIFs is that unlike gSIFs, they show marked systematic variations along their lengths in structural and functional features, include fibre diameter, [158,174,175] myofibrillar size [158,175], mitochondrial volume [175,176], sarcoplasmic reticulum volume [175] myosin ATPase histochemistry [177] and expression of MyHC genes [135,136,137,138,139]. The pattern of MyHC expression of these fibres is listed in the Table 2. The differences in MyHC composition of oSIFs and oMIFs indicate that they differ in speed, but these fibre types share the common feature that they express their respective fastest MyHC(s) in their central segments, flanked by end segments co-expressing several slower MyHCs.

It has recently been proposed that the functional significance of variations in MyHC expression of the central and end segments of oSIFs and oMIFs is that they are instrumental in linearizing the saccade [139]. At the commencement of a saccade, the antagonist must relax and be lengthened rapidly to allow the agonist to accelerate the eyeball. The relaxation rates of the central segments of the antagonist oSIF and oMIF units containing EO and α-cardiac MyHCs, respectively, would rapidly yet smoothly reduce the viscous load on the contracting agonist motor units, thus facilitating the initial angular acceleration of the eyeball. The twitch-like feature of the endplate region of oMIFs probably also contributes to faster relaxation. The relaxation rate of canine oMIFs is enhanced by the association of MLC1_E/A with β-slow MyHC in oMIFs whereas in the gMIFs, β-slow MyHC is associated with MLC1_S [178]. Without the fast, central segments, the slower cross-bridges of the antagonist fibres would resist rapid lengthening by developing high tensions [179]. Deceleration of the eyeball towards the end of the saccade is promoted by the end segments of oSIFs and oMIFs, which express a range of kinetically slow MyHCs. Stretching these slow, attached cross-bridges in the end segments of oSIF and oMIF would produce a high but progressively decreasing viscous load to decelerate the eyeball.

Variation in MyHC expression along the length also occurs in gMIFs. These fibres express α-cardiac and β-slow MyHCs in their central segment but the end segments additionally express slow to very slow isoforms: embryonic, slow-tonic, nmMyH IIB MyHCs. At the end of a saccade, passive tension of the stretched antagonist is transmitted along gMIFs to the palisade endings due to the very slow relaxation rates of these MyHCs. The resulting axon reflex helps to augment the slowly rising post-saccadic tension of the antagonist to match the post-saccadic fall in tension of the agonist to maintain fixation at the new location [89].

14. Regulation of MyHC Expression in EOM

The role of neural impulse activity on MyHC regulation in the EOM has been studied using botulinum toxin-mediated denervation [180] and in transplantation studies of EOMs regenerating under the influence of different types of nerves [89]. Botulinum toxin blocks acetylcholine release at the neuromuscular junction, bringing about a prolonged effective denervation followed by a slow recovery of function associated with the sprouting of terminal axons and the formation of new neuromuscular junctions. Following administration of this toxin to EOM in adult rats, SDS-PAGE revealed that EO MyHC was permanently abolished and 2B MyHC drastically reduced while 2A and 2X MyHCs dramatically increased 5 months after treatment with the toxin, with only partial recovery of the proportion of 2B MyHC after 8 months [180]. The complete loss of EO MyHC and the very slow partial recovery of MyHC expression profile may be related to the loss of high frequency impulses. This may be due to the failure of the regenerating endplates to transmit high frequency impulses, but may also be related to a prolonged impairment of the retrograde transport of neurotrophins to sustain the appropriate neural inputs to the oculomotor neurons to generate the normal range of impulse patterns.

Rabbit EOMs regenerating in situ and in fast limb muscle beds after freeze injury were compared using immunohistochemical analyses [89]. Regenerated EOMs innervated by limb fast muscle nerves strongly express the relatively slow neonatal, β-slow/slow-tonic and 2A MyHCs but not the faster MyHCs, even in the long term, whereas in situ regenerates innervated by the oculomotor nerve are able to express not only the slower MyHCs within the repertoire, but also the much faster 2X, 2B and EO MyHCs. These experiments suggest that the capacity of in situ regenerates to express the fast MyHCs is associated with the availability of a range of high to very high frequency impulses from oculomotor neurons.

The expression of the full range of MyHCs in in situ regenerates may have been facilitated by the selective reinnervation of regenerating SIFs and MIFs by their respective motoneurons. Selective reinnervation of slow tonic and fast twitch muscle fibres by their respective original nerve fibres have been reported in avian [181] and amphibian [182] muscles during reinnervation after their denervation. It is thus possible that tonic MIF motoneurons would selectively reinnervate regenerating MIFs while phasic SIF motoneurons selectively reinnervate regenerating SIFs. This will result in the retrograde transport of appropriate neurotrophic factors from MIFs and SIFs to ensure the delivery of the normal wide range of neural impulse frequencies and patterns of ocular motoneurons [169] to induce the expression of the full range of EOM MyHCs in the various fibre types. Low frequency tonic impulse patterns are postulated to regulate the expression of MyHCs at the slower end of the kinetic range (embryonic, neonatal, slow B, β-slow and 2A MyHCs) and high frequency phasic impulse patterns regulate the expression of the fastest MyHCs within the EOM repertoire, namely, 2X, 2B and EO. Motoneurons with firing patterns between these extremes show phasic and tonic activities to varying degrees and are postulated to control the expression of MyHCs in a frequency-dependent manner, the more phasic with higher frequencies control the faster MyHCs while the more tonic with lower frequencies regulate the slower MyHCs [89]. During spontaneous eye movements, the discharge characteristics of oculomotor neurons are characterized by a high frequency pulse followed by a slide of decreasing frequency and then a lower frequency step [169]. The delivery of impulses with a variety of frequencies to the same motor unit could explain the coexpression of multiple MyHCs in gSIFs.

The functional significance of the above impulse pattern hypothesis is that the very signals used to drive the various ocular movements are instrumental in equipping the different EOM motor units with appropriate MyHCs, and thus contractile properties to accomplish their tasks. In the EOM, the low-frequency impulse patterns of tonic motoneurons required for generating the mechanical characteristics for controlling eye fixation, tracking and vergence would induce the expression of MyHCs within the slow end of the kinetic spectrum, leading to relatively slow contracting, low power and economic motor units appropriate for these tasks. The high-frequency bursts of phasic motoneurons necessary for generating the mechanical features of large saccades and quick phases of vestibulo-ocular reflexes would induce the fastest MyHCs, leading to fast and powerful motor units suitable for rapid eye movements.

The notion that the impulse pattern needed to generate the desired mechanical activity is instrumental in inducing the appropriate MyHC also seems to apply in the case in limb muscle. The neural impulse pattern to rat slow soleus needed to generate sustained muscle tension is characterized by a sustained activity at low frequencies [183]. This chronic low frequency stimulation (CLFS) controls β-slow MyHC expression in this muscle and can convert other muscle fibre types into β-slow fibres (see later). Impulses delivered to the fast extensor digitorum longus (EDL) muscle, which predominantly express the three fast MyHCs, is characterized by high frequencies and has 2 subtypes, one with short bursts of high frequencies needed to generate powerful, brief bursts of tension; this impulse pattern supports 2B MyHC expression in denervated EDL. The other subtype is characterized by long bursts of high frequency needed to generate prolonged fast contractions; this pattern supports the expression of 2A/2X MyHCs but suppresses 2B MyHC in denervated EDL [184].

The above discussion does not address the localizations of slow MyHCs at the end-segments and of fast MyHCs in the central segments of oMIF, oSIF and gMIF, which are functionally very important. Future work needs to investigate how MyHC expression in the central and end segments of these fibre types is differentially regulated.

Relatively little is known about the role of thyroid hormone on MyHC expression in EOMs. It seems likely that thyroid hormone would facilitate the postnatal maturation of EOMs as it does in limb and other craniofacial muscles. In the adult rabbit, hyperthyroidism significantly decrease EOM mass, the total number of fibres, and the mean cross-sectional area of the fibres. Immunohistochemical analysis using antibodies to fast, slow, embryonic and neonatal MyHCs revealed that the percentages of neonatal and embryonic MyHC-positive fibres decreased, while the percentages of β-slow-positive fibres significantly increased in both global and orbital layers and fast MyHC-positive fibres were significantly reduced in both the central and end segments of the orbital layer fibres [185]. Since EOM fibres express 11 MyHCs and fibres co-express multiple MyHCs and the antibodies used in this study were deficient in number and specificity, these results are difficult to interpret. It is not possible to assess whether thyroid hormone shifted the expression of 2A MyHC towards 2B MyHC as it does in limb, jaw and laryngeal muscles (see later). The onerous task of clarifying the role on thyroid hormone on MyHC expression in EOMs would require the use of a comprehensive set of antibodies specific against each of the 11 MyHC isoforms and include analysis of changes along the length of various fibre types!

15. Developmental Origins of Jaw Muscles

Muscles that move the jaw develop from myogenic cells from the first branchial arch. These muscles fall into two functional groups: the jaw-closer (temporalis, masseter, medial pterygoid and the superior head of the lateral pterygoid) and jaw-openers (mylohyoid, anterior digastric and the inferior head of the lateral pterygoid). Jaw closers develop from cells in the dorsal portion of the first arch which derive from cranial paraxial mesoderm, while jaw-openers develop from mesodermal cells in the ventral portion of the first arch which derive from the lateral splanchnic mesoderm [186]. Pitx2 regulates transcription factors that specify first branchial arch myoblasts. It acts to assure the expression of pre-myogenic genes Tbx1, capsulin (Tcf21), and MyoR (musculin, Msc) in the first arch-derived muscles [187]. The Tbx1 gene commits cranial paraxial mesoderm progenitor myoblasts to pharyngeal muscles [1,188], while the expression of MyoR or of capsulin is necessary for the myogenesis of the jaw-closer muscles. In the absence of both these genes, jaw-closer muscles are absent, but the jaw-opener muscles develop normally [189]. Besides giving rise to jaw-opening muscle, cells of the lateral splanchnic mesoderm also have cardiogenic potential and are characterized by the strong expression of transcription factor islet1 [190]. A set of transcription factors expressed in lateral splanchnic mesoderm progenitors form a regulatory gene network that coordinates normal craniofacial muscle and cardiac development [191].

16. Functional Demands on Mammalian Jaw Muscles

Jaw-closer and jaw-opener muscles represent two distinct muscle allotypes with different myosin expression profiles. Jaw-closers provide the power behind the specialized bony and dental apparatus designed for the procurement and mastication of food. Across species, in sharp contrast to EOMs, functional demands on jaw-closing muscles are extremely varied, having to cope with the different lifestyles, diets and eating habits of the animals. These demands range from requiring high-force bite for hunting in carnivores to economy of energy expenditure for sustained mastication in ruminants. Consequently, myosin isoforms expressed in jaw-closers of different species vary widely, ranging from the high force jaw-specific masticatory myosin to one or more myosins of various speeds and powers found in limb and cardiac muscles. The functional load on jaw-opening muscles, however, is relatively constant and light, and they express myosin isoforms in common with limb muscles [192,193,194].

17. Fibre Types in Jaw-Closing Muscles of Carnivores

Rowlerson and co-workers first showed that muscle fibres in cat jaw-closers express a jaw-specific masticatory myosin with unique MyHCs and MLCs. Cat masticatory MyHC (MYH16) [20] and MLC2_M (MYL5) [40,195] have been sequenced and shown to be of very ancient origin, the masticatory MyHC gene is the first among mammalian MyHC genes to diverge from ancestral forms [20]. Masticatory MLC1_M (MYL4) is identical to the embryonic/atrial MLC1 (MLC1_E/A) [30]. Cat masticatory fibres also express a jaw-specific mMyBP-C [80,81] and m-Tm [81,196].

Jaw-closers of carnivores also contain jaw-specific slow fibres which differ histochemically [192] and immunohistochemically [197] from limb slow fibres. These jaw-slow fibres express the same β-slow MyHC as in limb slow fibres, but differ in MLC composition, expressing MLCs identical to those associated with masticatory MyHC [33,95].

As will be discussed below, masticatory fibres are associated with very high force of contraction to generate a strong bite while jaw-slow fibres are able to relax rapidly to permit the jaw to open wide rapidly prior to jaw closure.

18. Ontogeny of Jaw-Closing Muscles in Carnivores

In the dog, the temporalis muscle in utero expresses developmental MyHCs and MLCs similar to those of limb muscle during early myogenesis but begins to express masticatory MyHC and MLC isoforms two weeks postpartum [198]. Detailed immunohistochemical analysis of cat masseter muscle during perinatal development shows that there are four developmentally distinct myotube types, each characterized by a specific sequence of myosin gene expression during perinatal development [199]: (1) slow primaries which initially express embryonic and β-slow MyHCs but not neonatal MyHC and end up expressing β-slow MyHC at maturity, (2) masticatory primaries that initially express embryonic, neonatal and β-slow MyHCs but postnatally replace these with masticatory MyHC, (3) slow secondaries, which initially also express embryonic and neonatal MyHCs, postnatally replace these with β-slow MyHC with or without masticatory MyHC, ending up expressing only β-slow MyHC at maturity, and (4) masticatory secondaries, which initially express embryonic and neonatal MyHCs, which are postnatally replaced by masticatory MyHC [199]. In the developing cat posterior temporalis, which is composed homogeneously of masticatory fibres in the adult, only masticatory primary and masticatory secondary myotubes are present [200]. The posterior temporalis is homologous to the white region of limb fast muscle which is composed homogeneously of fast fibres and develop from fast primary and fast secondary myotubes [201].

The four types of myotubes in developing cat jaw-closing muscles are homologous to the four types of myotubes in developing limb muscle [201]. During limb muscle development, the fast primary and fast secondary myotubes postnatally express β-slow MyHC and 2A MyHC, respectively, but under the postnatal surge of thyroid hormone, they both express 2B MyHC at maturity. However, during hypothyroidism in the adult they revert to expressing β-slow MyHC and 2A MyHC respectively [202]. The 2B MyHC expressing fibres in the mature animal derived from fast primary and fast secondary myotubes are not the same but constitute distinct ontotypes which retain their intrinsic myotube derived properties in adult life: under hypothyroidism, only fibres derived from fast primaries express β-slow MyHC [124]. It is likely that thyroid hormone and neural impulse patterns play the same roles in the maturation of carnivore jaw-closers as in limb muscles, and that the notion of myotube ontotype also applies to craniofacial muscles. Of the two types of myotubes in the homogeneously masticatory fibres of cat posterior temporalis, only masticatory primaries express β-slow MyHC during development [200]. I postulate that the postnatal surge of thyroid hormone is required to induce the expression of masticatory MyHC in both myotube types, and that following hypothyroidism in the adult, only fibres of masticatory primary myotube origin will express β-slow MyHC. This would be analogous to the 2b fibres of fast primary ontotype expressing β-slow MyHC under hypothyroidism [202]. The apparent muscle and fibre type specificities of the changes in MyHC gene expression in response to changes in thyroid hormone level [203,204] are likely due to differences in muscle fibre ontotype.

19. Mechanical Properties of Masticatory Fibres of Carnivores

Since cat masticatory fibres have a very short contraction time [92,205] and masticatory myosin has a high ATPase activity [28], which normally connotes high speed [10], these fibres were thought to be superfast contracting and masticatory myosin was initially known as superfast myosin. However, measurement of both dynamic stiffness [33] and unloaded shortening velocity [206] indicated that masticatory fibres of cat and dog are comparable in speed of contraction to limb 2a fibres.

The rapid development of force indicated by the very short contraction time may be attributed to the high Ca²⁺ sensitivity [207] and the high proportion of ON cross-bridges along thick filaments revealed by X-ray diffraction studies [41]. A similar acceleration of the rate of force development associated with cross-bridge detachment from the thick filament occurs during post-tetanic potentiation of the fast muscle twitch [208]. This is also associated enhanced ON cross-bridges [78] due to the phosphorylation of MLC2_F leading to the destabilization of the IHM on the thick filament. The swinging out of cross-bridges towards thin filaments in resting masticatory fibres may result from a structural feature of MLC2_M resembling phosphorylated MLC2_F in destabilizing the IHM. The mMyBP-C may also play a role in destabilizing the IHM and enhance Ca²⁺ sensitivity.

Masticatory fibres develop about 40-60% more force per cross-sectional area compared with limb fast fibres [206,209]. This attribute is highly appropriate for a carnivorous lifestyle but is associated with a higher tension-cost [209]. The basis of the high force is thought to be an increase in cross-bridge attachment rate coupled with a matching decrease in detachment rate [206], but a model of masticatory myosin cross-bridge cycling kinetics that also explains high ATPase activity and high-tension cost is lacking. The possible role of mMyBP-C in modulating cross-bridge function requires clarification by future work.

Another highly desirable property of a jaw-closing muscle for a carnivore would be the ability to develop a very high tension when stretched while active, as it would help to prevent a struggling prey from escaping. Stretching an isometrically contracting muscle leads to an increase of force [210] which has been attributed to the recruitment of myosin heads that exhibit fast attachment to, and detachment from actin in a cycle that does not involve ATP splitting [211]. It is thus important for future work to determine whether lengthening of active masticatory fibres produce higher forces than limb-fast fibres.

20. Mechanical Properties of Jaw-Slow Fibres of Carnivores

The fact that jaw-slow myosin is associated with masticatory MLCs leads to very different kinetic properties compared with limb-slow fibres. Masticatory MLC1 or MLC1_E/A has a weaker interaction with actin compared with slow MLC1_s of limb slow fibres [32]. This raises the dynamic stiffness parameter, f_min, of jaw-slow fibres to tenfold higher than that of limb slow fibres [33]. This parameter is sensitive to rate constants for the power-stroke and the rate of cross-bridge detachment [212]. Further, the temperature sensitivity of f_min is reduced relative to that of limb-slow fibres, indicating a reduced activation energy for the cross-bridge cycling, which reflects a reduced stability of the attached crossbridge [33] and accelerated cross-bridge detachment rate, leading to a more rapid rate of relaxation.

A function of jaw-slow fibres in jaw-closing muscles is to produce a sustained force for hold the jaw against gravity. The functional significance of the expression of MLC1_E/A in jaw-slow fibres in jaw-closers appears to be to enable a carnivore to rapidly open the jaw prior to seizing a prey.

21. Neural Regulation of Masticatory and Jaw-Slow Fibres of Carnivores

The roles of cell lineage and innervation in regulating the expression of masticatory and jaw-slow myosins and other myofibrillar proteins gleaned from transplantation experiments have been referred to earlier in connection with the notion of muscle allotype. Those experiments [92] suggest that the expression of masticatory and jaw-slow myosin is regulated by the nerve to fast and slow muscle respectively. The induction of β-slow MyHC and the suppression of masticatory MyHC in cat temporalis regenerates innervated by the limb slow nerve [92,93] suggest that these changes are brought about by CLFS mediated by the tonic motoneurons innervating slow limb muscle. This has been confirmed by the transformation of masticatory fibres into jaw-slow fibres by CLFS of the cat temporalis muscle [213]. It is likely that the molecular mechanism involved here is the same as that which transform limb fast fibres into β-slow fibres. In this mechanism, the elevated intracellular Ca²⁺ concentration due to CLFS activates the phosphatase calcineurin, which dephosphorylates the nuclear factor of activated T cells (NFATc1) to enable it to enter the nucleus to interact with myocyte enhancer factor 2 (MEF-2C) to induce β-slow MyHC expression [214,215,216,217]. The hypothesis that jaw-slow fibres are also regulated by the calcineurin/NFAT pathway requires confirmation and how CLFS suppresses masticatory myofibrillar proteins requires future elucidation.

The nerve to fast limb muscle may also regulate masticatory MyHC expression using the same transcription factors employed in regulating fast MyHC expression. Recent work has shown that the expression of fast muscle genes in developing fast limb fibres requires the transcription factor Maf, the expression of which involves the operation of the L-type Ca²⁺ channel and the elevation of intracellular Ca²⁺ level during contraction [218]. The induction of 2B MyHC expression by neural activity is due to the binding of Maf to the 2B MyHC gene promoter [218,219]. Since nerve to fast muscle also regulates masticatory fibres, it would be interesting to investigate whether Maf is involved in the regulation of masticatory fibre genes, and whether a Maf binding motive exists in the promotor region of the masticatory MyHC gene.

22. Expression of Masticatory Myosin among Vertebrates

Masticatory myosin expression is uniquely confined to jaw-closing muscle, and it is not expressed in jaw-opening muscles of crocodile [193] and dog [192]. Jaw-opening muscles are derived from myogenic cells in the ventral portion of the first branchial arch and belong to a different allotype. Masticatory myosin expression is widespread among carnivorous vertebrates and nut eating mammals. These include the shark [90], crocodile [193], eutherian and marsupial carnivores, bandicoots and possums [95,220,221], chiropterans [222], some rodents [223] and some primates [194,222,224]. The feeding habits of these animals vary widely, and mechanical properties of their jaw-closers may well differ. Currently, we only have kinetic properties of jaw-closers in cats and dogs. The likely possibility that properties of masticatory myosin in different species may vary, for example, that it may be faster in small animals, as other MyHCs are, has not been investigated. However, extensive heterogeneity exists in tropomyosin and troponin T isoform expression in jaw-closing muscles between carnivores, rodents, marsupials and reptiles [225]. It has been suggested that differences in thin-filament-mediated muscle activation evolved to accommodate markedly different feeding styles that may require high force generation in some species and high speed in others. Rodents predominantly express β-Tm, and this would reduce Ca²⁺ sensitivity to permit rodents to nibble rapidly [225].

23. Phylogenetic Plasticity of Mammalian Jaw-Closing Muscles

Mammals evolved from carnivorous reptilian ancestors that expressed masticatory myosin in jaw-closing muscles. While poikilothermic reptiles with low metabolic rate hardly need to masticate their food for fast absorption of nutrients, it is a different matter for homeothermic mammals with their high metabolic rate. There is thus a functional demand in mammals to accelerate digestion by mastication of their food. During the mammalian radiation into various ecological niches and eating different types of food, the acquisition and mastication of which requires evolutionary changes not only in jaw and dental anatomy, but also in myosin isoforms and fibre types expressed. Some eutherian (carnivores, chiropterans, primates, rodents) and marsupial (dasyurids, peramelids, diprotodonts, didelphids) taxa retained masticatory myosin expression where high force in jaw-closers remained functionally advantageous to their lifestyle and diet [90]. However, some members of these taxa have extended their myosin expression repertoire or replaced masticatory myosin with other isoforms. Several marsupial species express masticatory fibres and α-cardiac/β-slow hybrid fibres, the ratio of masticatory to hybrid fibres being correlated with the amount of vegetable matter in their diet [221]. Among primates, the baboon extends the repertoire to comprise masticatory, 2A and β-slow myosins, while the sooty mangabey expresses masticatory, 2A, α-cardiac, β-slow myosins [224,226]. Human jaw-closers express 2X, 2A, α-cardiac β-slow, and neonatal myosins [227,228,229] but no longer express masticatory myosin, there being a frameshift mutation in the masticatory MyHC gene [230]. Of considerable interest is the fact that humans continue to express MLC1_E/A [231], which is associated with both masticatory and jaw-slow fibres of carnivores. Among carnivora, the red panda, which is no longer carnivorous, completely replaced masticatory myosin with limb fast isoforms [194], as has Miniopterus schreibersii among chiropterans [222].

Herbivorous animals that spend much of the day grazing and chewing the cud in ruminants have completely replaced masticatory myosin, which has a high tension-cost, with the more economic cardiac isoforms, expressing β-slow MyHC in ruminants like sheep and cattle [222,232,233] and α-cardiac MyHC in non-ruminants like macropods [243]. Though macropods and ruminants are both foregut fermenters, the former do not have a four-compartment stomach of ruminants to facilitate digestion [234]. Relative to the slow fibres of ruminants, the higher speed and power associated with α-cardiac fibres in macropods ensure rapid comminution of food into fine particles necessary for efficient fermentation without the benefit of rumination.

Mammals that feed on diets with a wide range of textures generally have jaw-closing muscles expressing several different myosin isoforms to generate fibres with a range of kinetic properties. The rat [235], hedgehog [236] and guinea pig [237] express the four limb myosin isoforms while the red squirrels and flying squirrels express limb fast and neonatal myosins [223]. In the rabbit, α-cardiac myosin is expressed in one-third of the jaw-closer fibre population, the rest express 2A and β-slow myosins [227,238].

The expression of myosins in jaw-closers of marsupial mammals illustrate well the adaptation of myosin expression to varying masticatory functional demands. The dasyurids, which are exclusively carnivorous [239,240], express only masticatory myosin in jaw-closers. Bandicoots and possums feed on varying proportions of insects and vegetable matter. Their jaw-closers contain a mixture of masticatory fibres and hybrid α-cardiac/β-slow fibres, the ratio of masticatory to α-cardiac/β-slow varies with the type of diet [221]. Bandicoots are predominantly insectivorous and have the higher proportion of masticatory fibres than possums. Brushtail possums are more frugivorous than folivorous [241] and have more masticatory fibres than ringtail possum, which feed on softer vegetable matter [242]. Kangaroos are herbivorous, and have completely suppressed masticatory MyHC, expressing α-cardiac and very little β-slow MyHC [243].

The extreme versatility of the jaw-closing muscle allotype in expressing such a variety of myosins in different animals pose interesting problems of how these patterns of myosin expression are achieved at the molecular level. Future work would need to investigate the molecular basis of the phylogenetic plasticity: how the network of transcription factors that specify the masticatory muscle allotype interact with the regulatory regions of the relevant MyHC and MLC genes in different species to bring about such diverse patterns of expression.

24. Development and Regulation of Myosin Expression in Jaw-Closing Muscles in Animals Not Expressing Masticatory Myosin

The prenatal development of rat masseter reveals that the patterns of MyHC expression during myogenesis are similar to those in limb muscles [116]. All primary myotubes stain with anti-β-slow myosin and anti-embryonic/neonatal MyHC antibodies, a small proportion of these myotubes (slow primaries) become β-slow fibres in the mature animal while most primary myotubes (fast primaries) become fast fibres. All secondary myotubes are negative with anti-β-slow myosin antibody but positive with anti-embryonic/neonatal MyHC antibody (fast secondaries) that mature into fast fibres, there being no slow secondary myotubes.

Masticatory muscles of rodents are subject to neural and hormonal regulation. Reducing functional load tends to lead to a shift towards fatigable 2b fibres while increasing functional load tends to shift towards fatigue resistant 2a and β-slow fibres. In the rat masseter, a shift of 2a fibres towards 2b fibres occurs in animals on a soft diet relative to those on a hard diet, the change being associated with reduced electromyographic activity in the masseter of rats on soft diet [244,245]. Similar changes in MyHC expression have also been observed at the mRNA level [246]. Rabbits on a soft diet also show a reduction of β-slow and 2b fibres with increased 2a fibres [247] or reduced slow fibres co-expressing β-slow and α-cardiac MyHCs [248]. On the contrary, increasing daily activity of rat masseter by increased occlusal vertical dimension leads to an increase in 2B MyHC mRNA and a decrease in 2A MyHC mRNA [249] and the corresponding proteins [250]. Increasing functional load in the rat also increases masseter β-slow MyHC mRNA, which is completely inhibited by cyclosporin A, an inhibitor of calcineurin [251]. This suggests that the calcineurin/NFAT pathway is involved here as it is in the neural regulation of β-slow MyHC in limb muscle via CLFS. Similarly, increasing functional load in the guinea pig leads to a shift towards β-slow myosin expression as indicated by a reduced masseter myosin ATPase activity and a reduced average thin filament sliding velocity of masseter myosin measured by in vitro motility assays [252].

In some rodents, fibre type distribution in jaw-closing muscles show sexual dimorphism, the male animals have more powerful jaw-closers than females. In the mouse, males have twice as many jaw-closer fibres containing the 2B MyHC as females, which have twice as many fibres containing the 2A MyHC as males [253]. Similarly in the rat, there are three times more 2b fibres in the masseter of males compared with females [254]. In rabbit jaw-closers, males have more 2a fibres and fewer α-cardiac/β-slow fibres than females [238]. Testosterone replacement in castrated male rabbits decreases the proportion of α-cardiac/β-slow fibres and increases that of 2a fibres, confirming the role of testosterone in generating the sexual dimorphism in fibre type distribution [255]. In the new-born guinea pig, both male and female temporalis muscles contain a fast-red, presumably 2A MyHC. At puberty, the male began to replace the fast-red isoform with a fast-white isoform, presumably 2X/2B MyHC, accompanied by a rise in testosterone levels. Castration of the male reverses this change while testosterone treatment of the female induces a shift towards fast-white MyHC [237]. The temporalis muscle of the baboon also shows sexual dimorphism, females have more β-slow fibres than males [224]. Sexual dimorphism in jaw muscles contrasts with limb muscles in which MyHC expression does not respond to sex hormones [256], consistent with the allotype difference between jaw and limb muscles.

In the rat masseter, thyroid hormone has been shown to shift the expression of 2A MyHC mRNA towards 2B MyHC mRNA, as it does in limb muscles [203]. However, histochemical analysis of rat masseter muscle reportedly failed to demonstrate a thyroid influence on fibre type distribution [257], but the method used was inadequate for discriminating 2a from 2b fibres. Future work using immunohistochemical methods will be needed to clarify the role of thyroid hormone on MyHC regulation in jaw-closing muscles in various species.

Acute adrenergic stimulation of limb fast and slow muscles enhances twitch and tetanic force [258]. Sympathetic nerve stimulation of rabbit jaw-closing muscle has a similar effect [259]. The enhanced force would be beneficial to an animal involved in self-defence, but little is known about the effects of acute adrenergic stimulation on jaw-closing muscles in other species. However, chronic adrenergic stimulation has been shown to induce a shift towards faster MyHCs in the rat masseter: follow a 2-week treatment with clenbuterol, a lipophilic β₂-adrenoceptor (β₂-AR) agonist, an increase of 2B MyHC and a decrease in 2X and 2A MyHCs at the protein [260,261] and mRNA [251] levels occur. This is a direct effect of β₂-AR action rather than the result of changes in motor activity [260]. This shift from 2A to 2B MyHC expression is mediated by the Akt/mammalian target of rapamycin (mTOR) pathway [262].

25. Intrinsic Laryngeal Muscles and Their Functions

Intrinsic laryngeal muscles have evolved to subserve the highly specialized and complex functions of moving the vocal fold for airway protection, respiratory control and phonation. In mammals there are five intrinsic laryngeal muscles: thyroarytenoid (TA), lateral cricoarytenoid (LCA), interarytenoid (IA), posterior cricoarytenoid (PCA), and cricothyroid (CT). The laryngeal muscles are classically divided into (1) adductors, comprising TA, LCA, and IA, which close the glottis, (2) the abductor, PCA, which opens the glottis, and (3) the vocal fold tensor, CT. The TA has a vocalis division (TA-V) located within the vocal fold which is important in phonation, and an external division (TA-X) which adducts the vocal fold to adjust airway resistance to prevent rapid lung recoil during expiration. TA-X is also involved in reflex closure of the glottis, a movement of great importance in airway protection during sneezing and coughing. The PCA lowers airway resistance during inspiration by abducting the vocal fold, whereas the CT tenses the vocal cord and thus controls the pitch of the voice. The CT is also involved in dilating the glottis during inspiration. The various functional demands on the different laryngeal muscles within species require variations in fibre type composition to match. Respiratory control in animals of different body mass requires changes in kinetic properties of laryngeal muscles to deal with body mass related changes in basal metabolic rate.

26. Developmental Origins of Laryngeal Muscles

Laryngeal muscles are derived from myogenic cells from somites 1 and 2 which migrate to the branchial arches [263]. CT is derived from the 4^th branchial arch and has the potential of expressing only myosin isoforms found in limb muscles. All the other laryngeal muscles are derived from the 6^th arch and belong to a different allotype which has the potential of expressing the superfast myosin, EO, in addition to limb muscle myosins [102,264,265,266].

There appears to have been no studies on the early myogenesis of laryngeal muscles, but histochemical analysis of postnatal rat laryngeal muscles suggests that fibre maturation is influenced by innervation and thyroid hormone: denervation impairs the development of β-slow and 2a fibres while hypothyroidism impairs the differentiation of 2b fibres [267].

27. MyHC Expression Repertoire of Laryngeal Muscles

While the CT in most mammals expresses limb muscle myosin isoforms, the MyHC expression repertoire of other laryngeal muscles across species include EO, 2B, 2X, 2A, β-slow and neonatal MyHCs, but show systematic variations between species. The expression of EO MyHC in laryngeal muscles was first described in the rabbit [264]. In rat laryngeal muscles, an apparently laryngeal-specific MyHC was identified, initially known as 2L MyHC [265], but was subsequently shown to be identical to EO MyHC [266,268,269]. The high speed of contraction of intrinsic laryngeal muscles expressing EO MyHC in the rat is associated with elevated expression levels of Ca²⁺ reuptake-related proteins of the sarcoplasmic reticulum (Ca²⁺ ATPases, phospholamban and calsquestrins) in comparison to the limb muscle [270]. Neonatal MyHC has been reported to be expressed in bovine muscle [271] and human [272] laryngeal muscles, and low levels of mRNA for this MyHC and α-MyHC has been reported in human laryngeal muscle [273]. Human TA has been reported to express slow-tonic MyHC [272,274] but this has been disputed [275].

28. Variations in MyHC Expression in Laryngeal Muscles

Two types of variation in the pattern of MyHC expression are found in laryngeal muscles: variations between muscles of different function within species and variations in specific muscles between species. Within species, the adductor TA expresses faster MyHCs or contain more fast fibres than the abductor, PCA, which expresses faster MyHCs than the vocal fold tensor, CT. This has been verified in rat, rabbit, cat, baboon [276], goat [277] and human [278] laryngeal muscles.

Between species, there is a clear inverse relationship between body mass and the speed associated with the MyHCs expressed in laryngeal muscles, expression of the fastest MyHC within the repertoire progressively dropping out as body mass increases. EO MyHC is expressed in the TA and PCA of small animals like rat [265,279,280] and rabbit [102] but not in the larger cat and baboon. The fastest MyHC expressed in cat [102] and dog [281] is 2B, but it is not expressed in the larger baboon [102], cattle [271] and horse [282], in which the fastest MyHC is 2X. The CT expresses only MyHC isoforms and fibre types found in the limb muscles of the same species [102].

The literature on human laryngeal muscles is highly complex. Most reports show that these muscles express 2X, 2A and β-slow MyHCs [283,284,285], and mRNA analysis show that they do not express the faster 2B and EO MyHCs [273]. However, SDS-PAGE analyses revealed an unidentified “2L” MyHC component from laryngeal muscles [285], including the CT, but absent from female subjects [286]. More recent work suggests that 2B MyHC mRNA and protein are weakly expressed in some human laryngeal muscles, and immunohistochemical analysis revealing that 2B MyHC in humans is always co-expressed with β-slow, 2A or 2X MyHCs [287]. Therefore, it seems likely that “2L” MyHC is actually 2B MyHC, and this would also explain the high velocity of some human laryngeal fibres that exceed the velocity of the fastest human limb (2x) fibres [283]. The identification of “2L” MyHC in human CT with 2B MyHC rather than EO MyHC is coherent with the notion that CT is a distinct allotype which does not express EO MyHC. 2B MyHC is also likely to be the isoform thought to be EO MyHC expressed in laryngeal muscle of a 7-month-old infant but not expressed in limb muscle [288], since 2B MyHC is also not expressed in human limb muscles.

Human laryngeal muscles also show considerable variability in fibre type distribution and MyHC expression pattern between individuals [286]. As myosin expression in laryngeal muscles is subject to neural regulation (see later), variations in MyHC expression in humans could arise from different patterns of use, e.g., by singers versus ordinary people and by baritones versus sopranos. The possible expression of EO MyHC in human laryngeal muscle [285] is of interest in this connection. Although the highest impulse frequency of human laryngeal motor units recorded during a cough is 50 Hz [289], it is possible that humans by training can produce the very high frequency impulses to induce EO MyHC expression in laryngeal muscles. It would be interesting in future work to determine whether very high frequency stimulation could induce the expression of EO MyHC in laryngeal muscles of animals which do not normally express this isoform.

29. Functional Significance of Variations in MyHC Expression of Laryngeal Muscles within Species

The higher speed of contraction of the adductor TA relative to the abductor PCA and the CT in the same species may represent an evolu tionary adaptation to ensure the effectiveness of the protective closure of the glottis to avoid inspiration of foreign matter into the lungs. As the abductor is active during inspiration [290], to be effective in the protective closure of the glottis, the adductor needs to be faster and more powerful than the abductor.

An important feature of laryngeal muscle fibres is the prevalence of hybrid fibres containing multiple MyHC isoforms. This has been reported in rat, rabbit and human laryngeal muscle fibres [102,281,284,285]. This feature is probably due to the delivery of multiple MyHC regulatory impulse patterns to the same motor unit. Variations in the ratio of different MyHC isoforms in laryngeal motor units can provide a mechanism for generating laryngeal motor units with a range of speeds. For example, in the TA of the rat and rabbit, all or nearly all fibres contain EO/2B MyHCs [276]. The ratio of these MyHCs probably varies at the motor unit level, so that units with increasing ratios of EO/2B MyHCs would have increasing speeds of contraction. The recruitment of motor units of increasing speeds would help to meet the increase in respiratory frequency above the basal level during physical activity. Future work needs to investigate this possibility.

30. Regulation of MyHC Expression in Laryngeal Muscles within Species

Expression of MyHCs in laryngeal muscles within species are subject to neural and thyroidal regulation as in limb muscles. The earliest report suggesting that laryngeal muscles are subject to neural regulation came from the obser vation of fibre type grouping in these muscles of horses [291] which arises from denervation and reinnervation of muscle fibres due to recurrent laryngeal neuropathy, a common condition in horses [282]. More concrete evidence that neural traffic controls laryngeal MyHC expression has been provided by the observation that CLFS of denervated sheep PCA muscle leads to the conversion of fast fibres into β-slow fibres [292].

Depriving laryngeal muscles of neural traffic by denervation or interfering with neuromuscular transmission leads to changes in MyHC expression. Denervation of the PCA of in the rat [293,294] and human [295] leads to a slow-to-fast fibre conversion as β-slow fibres are deprived of the CLFS needed for maintaining β-slow MyHC expression, the denervated β-slow fibres now responding to the euthyroid state by expressing fast MyHCs. Further, in the rat TA, EO and 2B MyHCs are down-regulated following denervation, replaced by 2X MyHC [294], presumably because of the loss of the very high frequency impulses that regulate EO MyHC [89] and the high frequency, low amount stimuli needed for the expression of 2B MyHC [184]. Laryngeal motoneurons in the rabbit can deliver 200 Hz impulses [296]. In the rat, after a single injection of botulinum toxin to block neuromuscular transmission in laryngeal muscle, a shift of MyHC expression occurs from EO towards 2B and 2X during the recovery period [297], presumably due to the filtering out of the very high frequency neural impulses suggested for the regulation of EO MyHC expression. Laryngeal muscles of horses normally express 2X, 2A and β-slow MyHCs, but some horses with no laryngoscopic evidence of recurrent laryngeal neuropathy showing fibre type grouping and a virtual elimination of 2x fibres, presumably because of the filtering out of the high frequency high amount impulse patterns promoting 2X MyHC expression [184] due to subclinical recurrent laryngeal neuropathy [282].

Neural regulation of laryngeal muscle fibres has also been demonstrated by cross-innervation experiments. Slow-to-fast fibre transformation occurs in dog PCA and LCA following cross-innervation by the hypoglossal nerve [298]. In the rat, TA-X is normally composed solely of eo/2b fibres while TA-V and other muscles innervated by the recurrent laryngeal nerve contain predominantly 2x fibres. Following recurrent laryngeal nerve section and reinnervation of laryngeal muscles, there was a progressive transfor mation of 20% of TA-X eo/2b fibres into pure 2x fibres, suggesting that nerve fibres normally innervating 2x fibres cross-innervated eo/2b fibres of the TA-X and transformed them into 2x fibres [280].

The fibre types of the rat sternohyoid (SH), a somitic muscle, comprise β-slow, 2a, 2x, and 2b fibres, whereas the TA-X has only 2b/eo fibres. Following cross-innervation of these muscles, the SH retained β-slow and 2a fibres, greatly increased the proportion of the faster 2x, and 2b fibres but failed to express EO MyHC. In the cross-innervated TA, the SH nerve failed to induce β-slow and 2A MyHC expression and failed to suppress EO MyHC expression in 2b/eo fibres. However, 2x fibres amounting to 4.2% appeared de novo in the TA-X [101]. These results show that the repertoires for MyHC expression of SH and TA are determined by their muscle allotype.

Although pure eo fibres are virtually absent in rat TA, rabbit TA-V contained 19% of these fibres [102]. The existence of such a high proportion of pure eo fibres shows that EO MyHC is not always coregulated with 2B MyHC, but that a distinct sig nal, presumably very high frequency neural impulses suggested for the regulation of EO MyHC in EOM [89].

Thyroid hormone also has an influence on fast MyHC expression in laryngeal muscles similar to that in limb muscles: a shift towards faster isoforms. In the adult rat TA, which does not express 2A MyHC, hyperthyroidism shifts 2X MyHC towards 2B MyHC without influencing the level of EO MyHC, while in the PCA, hyperthyroidism shifts 2A and 2X MyHCs towards 2B MyHC. Hypothyroidism has the opposite effects [279]. The expression of EO MyHC is slightly increased in hyperthyroid in rat TA relative to that in hypothyroid animals [279]. The functional significance of the thyroid induced shift to a faster MyHC profile is that it helps to adjust respiratory function to match the enhanced metabolic effects of the hormone.

31. Functional Significance of Variations in MyHC Expression in Laryngeal Muscles between Species

The inverse relationship between body size and the speed of the MyHC expressed in laryngeal muscles serves to adjust inspiratory and expiratory airway resistances to match changes in respiratory frequency associated with changes in metabolic rate with body mass. The basal metabolic rate of eutherian and marsupial mammals is scaled approximately to (body mass)^0.75 [299,300,301,302]. McMahon, arguing theoretically from elastic similarity, concluded that metabolic rate should scale to (body mass)^0.75 and physiological cycles should scale to (body mass)^−0.25 [303]. To deliver sufficient oxygen to support of the metabolic rate, lung ventilation rate must at least be similarly scaled to body mass. Ventilation rate, the product of tidal volume and respiratory frequency, scales to (body mass)^0.80 [304], the allometric exponent slightly exceeds that for basal metabolic rate, thereby ensuring adequate ventilation to support the metabolic rate as body mass changes. Respiratory frequency required to support this ventilation rate is observed to scaled to (body mass)^−0.26 [304], closely conforming to McMahon’s hypothesis. This means that small animals have high respiration rates and consequently less time within which to regulate airflow during each breath. The laryngeal muscles in small animals should therefore be faster contracting than those of large animals. The speeds of limb and cardiac MyHC isoforms do increase with decreasing body mass but are optimized for locomotion and cardiac function, respectively, the rate of change is inadequate to match respiratory requirements. The negative exponents of the allometric equations relating the speeds of 2b and β-slow fibres to body mass (0.041 to 0.175) [305] fall far short of that for respiratory frequency of 0.26. To meet respiratory control requirements over the body mass range, shifts towards slower fibres in large animals and faster fibres in small animals are needed. Thus, large animals like horses [282] and baboons [102] reduce laryngeal muscle speed by expressing predominantly β-slow and 2A MyHCs while animals at the lower end of the size spectrum need to resort to recruiting faster MyHCs not expressed in their limb muscles: 2B MyHC in cats [102] and dogs [281] and EO MyHC in rats [280]. The contractile properties of laryngeal muscles across the species reflect these fibre type changes [91,306]. At the extremely low end of the body mass spectrum, β-slow and 2a fibres would be expected to disappear from laryngeal muscles, as they have in limb muscles of the shrew [307], while pure eo fibres would probably predominate in all laryngeal muscles of the shrew, exception perhaps in the allotypically different CT.

32. Regulation of MyHC Expression in Laryngeal Muscles between Species

Variations in MyHC expression in laryngeal muscles between species reflect changes in the properties of the cell lineage during phylogeny. The fact that rat TA does not express 2A and β-slow MyHCs is not due to lack of neural impulses supporting these MyHCs since cross-innervation by a nerve supporting these MyHCs failed to induce them in rat TA [101]. It is likely that failure to express EO MyHC in cats and dogs, and the failure to express EO and 2B MyHCs in baboons and horses are also not likely to be due to the lack of appropriate neural impulse patterns needed to express these MyHCs but are properties of the cell lineages. As body mass increases and the associated basal metabolic rate decreases during phylogeny, the molecular mechanisms for expressing fast MyHCs presumably become progressively less used and may eventually be lost through gene mutations, as in the case of 2B MyHC gene in the horse [308], while mechanisms regulating the slower MyHC are fortified. It remains possible that disused mechanisms for expressing fast MyHCs may survive in some animals. It would be interesting to determine whether the TA of the cat, which is near the lower end of the size spectrum that normally does not express EO MyHC, would respond to very high frequency stimulation by expressing EO MyHC.

33. Overview of Myosin Expression Mechanisms in Craniofacial Muscles

This review has highlighted the fact that the pattern of myosin expression in mammalian craniofacial muscles is principally influenced by the complex interplay of cell lineages, neural impulse patterns, thyroid and other hormones, functional demands and body mass. Even before myogenesis, myoblast progenitors of craniofacial muscles from different regions of the cranial mesoderm are channelled into specific progenitor lineages with different repertoires for MyHC expression during subsequent myogenesis. During myogenesis, embryonic and foetal myoblast lineages in craniofacial muscles form primary and secondary myotubes and express the same developmental MyHCs apparently in the same way as in limb muscles, but with very different patterns of gene expression in most craniofacial muscles during subsequent development. The various types of myotubes probably represent distinct ontotypes that determine their specific modes of response to neural and thyroid hormone influences as the ontotypes in limb muscle.

Neural impulse patterns regulate MyHC expression in craniofacial muscles in common with somitic muscles, enabling them to adjust their properties to changing functional demands. CLFS leads to the expression of β-slow MyHC in jaw and laryngeal muscles, as in limb muscle. The different impulse patterns for the regulation of specific fast MyHCs in limb muscles probably also apply to craniofacial muscles competent to express these MyHCs. The much more complex expression of the numerous MyHCs of EOMs is matched by the rich diversity of impulse patterns of ocular motoneurons. It is suggested above that during EOM myogenesis, different myotube ontotypes specify the impulse patterns necessary for controlling the specific MyHC they are destined to express. They do this by supplying specific neurotrophins to their innervating motoneuron via retrograde axoplasmic transport to specify the appropriate synaptic inputs to generate a variety of impulse patterns to induce different MyHC isoforms. This raises the question whether similar mechanisms are involved in generating specific impulse patterns for regulating MyHC expression in other craniofacial muscles.

Thyroid hormone promotes fast limb muscle development by suppressing embryonic and neonatal MyHCs and inducing the expression of fast MyHCs. In rat masseter and laryngeal muscles, thyroid hormone shifts the expression of 2A and 2X MyHCs towards 2B MyHC, just as it does in limb fast muscles. Thyroid induced shift in MyHC expression toward faster isoforms in laryngeal muscles helps to adjust the respiratory rate to the higher metabolic rate induced by the hormone. In jaw-closing muscles of carnivores, thyroid hormones may also be involved in the developmental transition from embryonic and neonatal MyHC expression to that of masticatory MyHC, but this has yet to be confirmed. Much future work will be needed to determine whether thyroid hormone is also involved in the regulation of MyHC expression in EOMs during postnatal development.

Functional demands on craniofacial muscles across the species vary considerably, the most complex being the demands on EOMs. To deal with demands to generate linearized saccades, smooth pursuit movements and steady fixations, EOMs expresses 11 MyHC isoforms ranging from the superfast EO MyHC to the very slowest nmMyH IIB, with variations in MyHC expression along the length in some fibre types. In addition, it evolved specialized global and orbital layers, multiple innervation and palisade endings. Although the functions of EOM are highly complex, they are quite similar across the species and there is relatively little variation in fibre types and repertoire of MyHC express in EOM fibres across the species.

Functional demands on jaw-closing muscles across different mammalian species vary most widely, mammals in different ecological niches need to adapt to the various methods of procuring and masticating a wide variety of foods. Mammals inherited the high force masticatory MyHC from their synapsid ancestors, but many taxa have replaced it with one or more of the cardiac and limb MyHCs with properties more appropriate for the acquisition and mastication of their food. Jaw-closing muscles across the species have the most varied pattern of MyHC expression, with an overall repertoire that includes the jaw-closer specific masticatory MyHC and all skeletal and cardiac MyHC isoforms.

A functional demand of laryngeal muscles is to meet the changing respiratory requirements as basal metabolic rate increases with decreases in body mass. Laryngeal muscles express limb MyHC isoforms and deal with this functional demand by shifting the MyHC expression profile towards slower isoforms in large animals and faster isoforms in small animals, even by expressing fast MyHC not expressed in their limb muscles. Airway protection in small animals demands a very fast laryngeal adductor and is met by extending the repertoire of MyHC expression to include EO MyHC.

34. Future Directions

Suggestions for future work on specific topics of interest in craniofacial muscles have been made passim in this review. Although the pattern of MyHC expression in different muscle allotypes and the variations in MyHC expression among animal species are reasonably well established, we know relatively little about the molecular mechanisms involved. One issue is whether the molecular mechanism regulating a specific MyHC in craniofacial muscle is the same as that in limb muscle. The neural regulation of β-slow MyHC via CLFS is apparently the same in jaw and laryngeal muscles as in limb muscle, and probably likewise for neural impulse patterns regulating fast MyHCs. Recently, the deletion of the large Maf (Mafa, Mafb and Maf) transcription factor family in mice has identified these factors as a major regulator for the expression of 2B MyHC in limb muscles [219]. It would be important to determine whether ablation of large Maf, which blocks the expression of 2B MyHC in limb muscles, would also blocks 2B MyHC expression in craniofacial muscles, and if so, what upstream factors in the myogenic cells of the various craniofacial allotypes turn on these Maf factors to induce 2B MyHC.

We also do not know the molecular mechanisms that enable the jaw-closing muscle cell lineage to express limb MyHC isoforms in the rat, α-cardiac MyHC in kangaroos, but β-slow MyHC in ruminants. The promoter region of the α-cardiac MyHC in kangaroos, for example, must directly or indirectly respond to some jaw-specific factor to induce α-cardiac MyHC in the jaw-closing muscles of kangaroos. Much work needs to be done to elucidate the cis-acting elements and trans-acting factors involved in the expression the MyHC genes in craniofacial muscles of different animal species.

Future work needs to examine the role of MyBP-C in modulating contractile properties of craniofacial muscles. Although sMyBP-C is known to be expressed in all human EOM fibres [87], its function is currently unknown. Based on studies on limb muscle [86], it is conceivable that in EOMs, the binding of phosphorylated N-terminal of sMyBP-C to thick filaments in gSIF would enhance the eyeball rotation force at the beginning of a saccade, while the binding of unphosphorylated sMyBP-C to thin filaments in the end segments of oMIF and gMIF would increase their stiffness and help to break eyeball rotation towards the end of a saccade. This would require the expression of an appropriate protein kinase to phosphorylate sMyBP-C in gSIF and possibly a phosphatase in oMIF and gMIF. In masticatory fibres, the N-terminals of mMyBP-C may weaken the IHM of masticatory myosins along thick filaments to bring about the observed swinging out of cross-bridges towards thin filaments [41].

Relatively little work has been done on the effect of adrenergic stimulation on the mechanical properties of craniofacial muscles besides that of Grassi et al. on force enhancement in rabbit masseter [259]. The enhanced force of masseter muscle following adrenergic stimulation may help to deliver an advantage in self-defence. In laryngeal muscles, β-adrenergic stimulation may result in force enhancement and accelerated relaxation rate as in limb muscles. This would be beneficial to an animal during a fight or flight situation by facilitating an enhanced respiratory rate.

The mechanism of action of adrenaline on muscle mechanics may involve MyBP-C. As β-adrenergic stimulation activates cAMP-activated protein kinase, which can phosphorylate sMyBP-C [86,309], this kinase is expected to phosphorylate sMyBP-C present in slow as well as in fast limb muscles following β-adrenergic stimulation. Phosphorylation of sMyBP-C would lead to the enhanced muscle force and accelerated the rate of relaxation [86], just as observed following β-adrenergic stimulation in fast and slow muscles [258]. It is thus highly likely that phosphorylation of sMyBP-C underlies the molecular basis for the mechanical response to β-adrenergic stimulation in craniofacial and limb muscles, but this needs confirmation by future work. MyBP-C isoforms expressed in laryngeal muscles has not even been investigated, though it is likely that sMyBP-C is expressed in these fibres as it is in fast and slow limb fibres as well as EOM fibres. Future work on the mechanical effects of adrenergic stimulation on EOMs, jaw and laryngeal muscles and their molecular bases would be of interest.

Funding

This research received no external funding.

Conflicts of Interest

The author declares no conflict of interest.

References

Sambasivan, R.; Gayraud-Morel, B.; Dumas, G.; Cimper, C.; Paisant, S.; Kelly, R.G.; Tajbakhsh, S. Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev. Cell 2009, 16, 810–821. [Google Scholar] [CrossRef]
Wachtler, F.; Jacob, H.J.; Jacob, M.; Christ, B. The extrinsic ocular muscles in birds are derived from the prechordal plate. Naturwissenschaften 1984, 71, 379–380. [Google Scholar] [CrossRef]
Couly, G.F.; Coltey, P.M.; Le Douarin, N.M. The developmental fate of the cephalic mesoderm in quail-chick chimeras. Development 1992, 114, 1–15. [Google Scholar] [CrossRef]
Bohnsack, B.L.; Gallina, D.; Thompson, H.; Kasprick, D.S.; Lucarelli, M.J.; Dootz, G.; Nelson, C.; McGonnell, I.M.; Kahana, A. Development of extraocular muscles requires early signals from periocular neural crest and the developing eye. Arch. Ophthalmol. 2011, 129, 1030–1041. [Google Scholar] [CrossRef]
Noden, D.M.; Francis-West, P. The differentiation and morphogenesis of craniofacial muscles. Dev. Dyn. 2006, 235, 1194–1218. [Google Scholar] [CrossRef]
Sperber, G.H. Craniofacial Embryology; Wright: London, 1989. [Google Scholar]
Sambasivan, R.; Kuratani, S.; Tajbakhsh, S. An eye on the head: the development and evolution of craniofacial muscles. Development 2011, 138, 2401–2415. [Google Scholar] [CrossRef]
Liu, Y.; Chu, A.; Chakroun, I.; Islam, U.; Blais, A. Cooperation between myogenic regulatory factors and SIX family transcription factors is important for myoblast differentiation. Nucleic Acids Res. 2010, 38, 6857–6871. [Google Scholar] [CrossRef] [PubMed]
Buckingham, M.; Rigby, P.W. Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev. Cell 2014, 28, 225–238. [Google Scholar] [CrossRef]
Barany, M. ATPase activity of myosin correlated with speed of muscle shortening. J. Gen. Physiol. 1967, 50, 197–218. [Google Scholar] [CrossRef] [PubMed]
Squire, J. Special Issue: The actin-myosin interaction in muscle: background and overview. Int. J. Mol. Sci. 2019, 20. [Google Scholar] [CrossRef] [PubMed]
Huxley, A.F. Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 1957, 7, 257–318. [Google Scholar] [CrossRef]
Desjardins, P.R.; Burkman, J.M.; Shrager, J.B.; Allmond, L.A.; Stedman, H.H. Evolutionary implications of three novel members of the human sarcomeric myosin heavy chain gene family. Mol. Biol. Evol. 2002, 19, 375–393. [Google Scholar] [CrossRef] [PubMed]
Moncman, C.L.; Andrade, F.H. Nonmuscle myosin IIB, a sarcomeric component in the extraocular muscles. Exp. Cell Res. 2010, 316, 1958–1965. [Google Scholar] [CrossRef]
Weiss, A.; Schiaffino, S.; Leinwand, L.A. Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity. J. Mol. Biol. 1999, 290, 61–75. [Google Scholar] [CrossRef]
McNally, E.M.; Kraft, R.; Bravozehnder, M.; Taylor, D.A.; Leinwand, L.A. Full-Length rat alpha and beta cardiac myosin heavy chain sequences - comparisons suggest a molecular basis for functional differences. J. Mol. Biol. 1989, 210, 665–671. [Google Scholar] [CrossRef] [PubMed]
Saez, L.J.; Gianola, K.M.; McNally, E.M.; Feghali, R.; Eddy, R.; Shows, T.B.; Leinwand, L.A. Human cardiac myosin heavy chain genes and their linkage in the genome. Nucleic Acids Res. 1987, 15, 5443–5459. [Google Scholar] [CrossRef]
Rossi, A.C.; Mammucari, C.; Argentini, C.; Reggiani, C.; Schiaffino, S. Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles. J. Physiol. 2010, Pt 2, 353–364. [Google Scholar] [CrossRef]
Mascarello, F.; Toniolo, L.; Cancellara, P.; Reggiani, C.; Maccatrozzo, L. Expression and identification of 10 sarcomeric MyHC isoforms in human skeletal muscles of different embryological origin. Diversity and similarity in mammalian species. Ann. Anat. 2016, 207, 9–20. [Google Scholar] [CrossRef] [PubMed]
Qin, H.; Hsu, M.K.; Morris, B.J.; Hoh, J.F.Y. A distinct subclass of mammalian striated myosins: structure and molecular evolution of 'superfast' or masticatory myosin heavy chain. J. Mol. Evol. 2002, 55, 544–552. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Yeoh, G.P.S. Rabbit skeletal myosin isoenzymes from foetal, fast-twitch and slow-twitch muscles. Nature 1979, 280, 321–323. [Google Scholar] [CrossRef]
Barton, P.J.R.; Buckingham, M.E. The myosin alkali light chain proteins and their genes. Biochem. J. 1985, 231, 249–261. [Google Scholar] [CrossRef]
Lowey, S.; Waller, G.S.; Trybus, K.M. Function of skeletal muscle myosin heavy and light chain isoforms by an in vitro motility assay. J. Biol. Chem. 1993, 268, 20414–20418. [Google Scholar] [CrossRef]
Greaser, M.L.; Moss, R.L.; Reiser, P.J. Variations in contractile properties of rabbit single muscle fibres in relation to troponin T isoforms and myosin light chains. J. Physiol. 1988, 406, 85–98. [Google Scholar] [CrossRef]
Stepkowski, D. The role of the skeletal muscle myosin light chains N-terminal fragments. FEBS Lett. 1995, 374, 6–11. [Google Scholar] [CrossRef] [PubMed]
Whalen, R.G.; Butler-Browne, G.S.; Gros, F. Identification of a novel form of myosin light chain present in embryonic muscle tissue and cultured muscle cells. J. Mol. Biol. 1978, 126, 415–431. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; McGrath, P.A.; Hale, P.T. Electrophoretic analysis of multiple forms of rat cardiac myosin: effects of hypophysectomy and thyroxine replacement. J. Mol. Cell Cardiol. 1978, 10, 1053–1076. [Google Scholar] [CrossRef] [PubMed]
Rowlerson, A.; Pope, B.; Murray, J.; Whalen, R.G.; Weeds, A.G. A novel myosin present in cat jaw-closing muscles. J. Musc. Res. Cell Motil. 1981, 2, 415–438. [Google Scholar] [CrossRef]
Barton, P.J.; Robert, B.; Cohen, A.; Garner, I.; Sassoon, D.; Weydert, A.; Buckingham, M.E. Structure and sequence of the myosin alkali light chain gene expressed in adult cardiac atria and fetal striated muscle. J. Biol. Chem. 1988, 263, 12669–12676. [Google Scholar] [CrossRef]
Reiser, P.J.; Bicer, S.; Patel, R.; An, Y.; Chen, Q.; Quan, N. The myosin light chain 1 isoform associated with masticatory myosin heavy chain in mammals and reptiles is embryonic/atrial MLC1. J. Exp. Biol. 2010, Pt 10, 1633–1642. [Google Scholar] [CrossRef]
Cohen-Haguenauer, O.; Barton, P.J.; Van Cong, N.; Cohen, A.; Masset, M.; Buckingham, M.; Frézal, J. Chromosomal assignment of two myosin alkali light-chain genes encoding the ventricular/slow skeletal muscle isoform and the atrial/fetal muscle isoform (MYL3, MYL4). Hum. Genet. 1989, 81, 278–282. [Google Scholar] [CrossRef] [PubMed]
Morano, I.; Haase, H. Different actin affinities of human cardiac essential myosin light chain isoforms. FEBS Lett. 1997, 408, 71–74. [Google Scholar] [CrossRef]
Hoh, J.F.Y. Li, Z.B.; Qin, H.; Hsu, M.K.; Rossmanith, G.H. Cross-bridge kinetics of fast and slow fibres of cat jaw and limb muscles: correlations with myosin subunit composition. J. Muscle Res. Cell Motil. 2007, 28, 329–341. [Google Scholar] [CrossRef]
Collins, J.H. Myoinformatics report: myosin regulatory light chain paralogs in the human genome. J. Muscle Res. Cell Motil. 2006, 27, 69–74. [Google Scholar] [CrossRef]
Nudel, U.; Calvo, J.M.; Shani, M.; Levy, Z. The nucleotide sequence of a rat myosin light chain 2 gene. Nucleic Acids Res. 1984, 12, 7175–7186. [Google Scholar] [CrossRef] [PubMed]
Kumar, C.C.; Cribbs, L.; Delaney, P.; Chien, K.R.; Siddiqui, M.A. Heart myosin light chain 2 gene. Nucleotide sequence of full length cDNA and expression in normal and hypertensive rat. J. Biol. Chem. 1986, 261, 2866–2872. [Google Scholar] [CrossRef] [PubMed]
Henderson, S.A.; Xu, Y.C.; Chien, K.R. Nucleotide sequence of full length cDNAs encoding rat cardiac myosin light chain-2. Nucleic Acids Res. 1988, 16, 4722. [Google Scholar] [CrossRef] [PubMed]
Kubalak, S.W.; Miller-Hance, W.C.; O'Brien, T.X.; Dyson, E.; Chien, K.R. Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis. J. Biol. Chem. 1994, 269, 16961–16970. [Google Scholar] [CrossRef] [PubMed]
Collins, C.; Schappert, K.; Hayden, M.R. The genomic organization of a novel regulatory myosin light chain gene (MYL5) that maps to chromosome 4p16.3 and shows different patterns of expression between primates. Hum. Mol. Genet. 1992, 1, 727–733. [Google Scholar] [PubMed]
Qin, H.; Morris, B.J.; Hoh, J.F.Y. Isolation and structure of cat superfast myosin light chain-2 cDNA and evidence for the identity of its human homologue. Biochem. Biophys. Res. Commun. 1994, 200, 1277–1282. [Google Scholar] [CrossRef] [PubMed]
Yamaguchi, M.; Takemori, S.; Kimura, M.; Tanishima, Y.; Nakayoshi, T.; Kimura, S.; Ohno, T.; Yagi, N.; Hoh, J.F.Y.; Umazume, Y. Protruding masticatory (superfast) myosin heads from staggered thick filaments of dog jaw muscle revealed by X-ray diffraction. J. Biochem. 2010, 147, 53–61. [Google Scholar] [CrossRef]
Close, R.I.; Luff, A.R. Dynamic properties of inferior rectus muscle of the rat. J. Physiol. 1974, 236, 259–270. [Google Scholar] [CrossRef] [PubMed]
Luff, A.R. Dynamic properties of the inferior rectus, extensor digitorum longus, diaphragm and soleus muscles of the mouse. J. Physiol. 1981, 313, 161–171. [Google Scholar] [CrossRef]
Asmussen, G.; Beckers-Bleukx, G.; Marechal, G. The force-velocity relation of the rabbit inferior oblique muscle; influence of temperature. Pflugers Arch. Eur. J. Physiol. 1994, 426, 542–547. [Google Scholar] [CrossRef] [PubMed]
Li, Z.B.; Rossmanith, G.H.; Hoh, J.F.Y. Cross-bridge kinetics of rabbit single extraocular and limb muscle fibers. Invest. Ophthalmol. Visual Sci. 2000, 41, 3770–3774. [Google Scholar]
McLoon, L.K.; Park, H.N.; Kim, J.H.; Pedrosa-Domellof, F.; Thompson, L.V. A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain colocalization. J. Appl. Physiol. 2011, 111, 1178–1189. [Google Scholar] [CrossRef]
Hilber, K.; Galler, S.; Gohlsch, B.; Pette, D. Kinetic properties of myosin heavy chain isoforms in single fibers from human skeletal muscle. FEBS Lett. 1999, (3. 3), 267–270. [Google Scholar] [CrossRef]
Reggiani, C.; Bottinelli, R.; Stienen, G.J. Sarcomeric myosin isoforms: fine tuning of a molecular motor. News Physiol. Scis. 2000, 15, 26–33. [Google Scholar] [CrossRef]
Weiss, S.; Rossi, R.; Pellegrino, M.A.; Bottinelli, R.; Geeves, M.A. Differing ADP release rates from myosin heavy chain isoforms define the shortening velocity of skeletal muscle fibers. J. Biol. Chem. 2001, 276, 45902–45908. [Google Scholar] [CrossRef]
Rossmanith, G.H.; Hoh, J.F.Y.; Kirman, A.; Kwan, L.J. Influence of V1 and V3 isomyosins on the mechanical behaviour of rat papillary muscle as studied by pseudo-random binary noise modulated length perturbations. J. Muscle Res. Cell Motil. 1986, 7, 307–319. [Google Scholar] [CrossRef]
VanBuren, P.; Harris, D.E.; Alpert, N.R.; Warshaw, D.M. Cardiac V1 and V3 myosins differ in their hydrolytic and mechanical activities in vitro. Circ. Res. 1995, 77, 439–444. [Google Scholar] [CrossRef]
Sciote, J.J.; Kentish, J.C. Unloaded shortening velocities of rabbit masseter muscle fibres expressing skeletal or alpha-cardiac myosin heavy chains. J. Physiol. 1996, Pt 3, 659–667. [Google Scholar] [CrossRef]
Yazaki, Y.; Raben, M.S. Effect of the thyroid state on the enzymatic characteristics of cardiac myosin. A difference in behavior of rat and rabbit cardiac myosin. Circ. Res. 1975, 36, 208–215. [Google Scholar] [CrossRef] [PubMed]
Bloemink, M.J.; Adamek, N.; Reggiani, C.; Geeves, M.A. Kinetic analysis of the slow skeletal myosin MHC-1 isoform from bovine masseter muscle. J. Mol. Biol. 2007, 373, 1184–1197. [Google Scholar] [CrossRef] [PubMed]
Bottinelli, R.; Canepari, M.; Reggiani, C.; Stienen, G.J. Myofibrillar ATPase activity during isometric contraction and isomyosin composition in rat single skinned muscle fibres. J. Physiol. 1994, 481 Pt 3, 663–675. [Google Scholar] [CrossRef]
Rossmanith, G.H.; Hamilton, A.M.; Hoh, J.F.Y. Influence of myosin isoforms on tension cost and crossbridge kinetics in skinned rat cardiac muscle. Clin. Exp. Pharmacol. Physiol. 1995, 22, 423–429. [Google Scholar] [CrossRef]
Close, R. Dynamic properties of fast and slow skeletal muscles of the rat during development. J. Physiol. 1964, 173, 74–95. [Google Scholar] [CrossRef]
Whalen, R.G.; Sell, S.M.; Butler-Browne, G.S.; Schwartz, K.; Bouveret, P.; Pinset-Harstom, I. Three myosin heavy-chain isozymes appear sequentially in rat muscle development. Nature 1981, 292, 805–809. [Google Scholar] [CrossRef]
Agbulut, O.; Noirez, P.; Beaumont, F.; Butler-Browne, G. Myosin heavy chain isoforms in postnatal muscle development of mice. Biol. Cell. 2003, 95, 399–406. [Google Scholar] [CrossRef]
Johnson, C.A.; Walklate, J.; Svicevic, M.; Mijailovich, S.M.; Vera, C.; Karabina, A.; Leinwand, L.A.; Geeves, M.A. The ATPase cycle of human muscle myosin II isoforms: Adaptation of a single mechanochemical cycle for different physiological roles. J. Biol. Chem. 2019, 294, 14267–14278. [Google Scholar] [CrossRef] [PubMed]
Schiaffino, S.; Rossi, A.C.; Smerdu, V.; Leinwand, L.A.; Reggiani, C. Developmental myosins: expression patterns and functional significance. Skeletal Muscle 2015, 5, 22. [Google Scholar] [CrossRef] [PubMed]
Matyushkin, D.P. Varieties of tonic muscle fibres in the oculomotor apparatus of the rabbit. Bull. Exp. Biol. Med. (Engl. Transl.) 1964, 55, 235–238. [Google Scholar] [CrossRef]
Bach-y-Rita, P.; Ito, F. In vivo studies on fast and slow muscle fibers in cat extraocular muscles. J. Gen. Physiol. 1966, 49, 1177–1198. [Google Scholar] [CrossRef]
Lennerstrand, G. Mechanical studies on the retractor bulbi muscle and its motor units in the cat. J. Physiol. 1974, 236, 43–55. [Google Scholar] [CrossRef] [PubMed]
Nelson, J.S.; Goldberg, S.J.; McClung, J.R. Motoneuron electrophysiological and muscle contractile properties of superior oblique motor units in cat. J. Neurophysiol. 1986, 55, 715–726. [Google Scholar] [CrossRef] [PubMed]
Pierobon-Bormioli, S.P.; Torresan, P.; Sartore, S.; Moschini, G.B.; Schiaffino, S. Immunohistochemical identification of slow-tonic fibers in human extrinsic eye muscles. Invest. Ophthalmol. Visual Sci. 1979, 18, 303–306. [Google Scholar]
Pierobon-Bormioli, S.; Sartore, S.; Vitadello, M.; Schiaffino, S. Slow myosins in vertebrate skeletal muscle. An immunofluorescence study. J. Cell Biol. 1980, 85, 675–681. [Google Scholar]
Close, R.; Hoh, J.F.Y. Effects of nerve cross-union on fast-twitch and slow-graded muscle fibres in the toad. J. Physiol. 1968, 198, 103–125. [Google Scholar] [CrossRef] [PubMed]
Morgan, D.L.; Proske, U. Vertebrate slow muscle: its structure, pattern of innervation, and mechanical properties. Physiol. Rev. 1984, 64, 103–169. [Google Scholar] [CrossRef]
Lee, L.A.; Barrick, S.K.; Meller, A.; Walklate, J.; Lotthammer, J.M.; Tay, J.W.; Stump, W.T.; Bowman, G.; Geeves, M.A.; Greenberg, M.J.; Leinwand, L.A. Functional divergence of the sarcomeric myosin, MYH7b, supports species-specific biological roles. J. Biol. Chem. 2023, 299, 102657. [Google Scholar] [CrossRef]
Stewart, M.A.; Franks-Skiba, K.; Chen, S.; Cooke, R. Myosin ATP turnover rate is a mechanism involved in thermogenesis in resting skeletal muscle fibers. Proc. Natl. Acad. Sci. USA 2010, 107, 430–435. [Google Scholar] [CrossRef]
Linari, M.; Brunello, E.; Reconditi, M.; Fusi, L.; Caremani, M.; Narayanan, T.; Piazzesi, G.; Lombardi, V.; Irving, M. Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments. Nature 2015, 528, 276–279. [Google Scholar] [CrossRef]
Fusi, L.; Brunello, E.; Yan, Z.; Irving, M. Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle. Nature commun. 2016, 7, 13281. [Google Scholar] [CrossRef]
Irving, M. Regulation of Contraction by the Thick Filaments in Skeletal Muscle. Biophys. J. 2017, 113, 2579–2594. [Google Scholar] [CrossRef] [PubMed]
Marcucci, L. Muscle mechanics and thick filament activation: an emerging two-way interaction for the vertebrate striated muscle fine regulation. Int. J. Mol. Sci. 2023, 24. [Google Scholar] [CrossRef]
Stull, J.T.; Manning, D.R.; High, C.W.; Blumenthal, D.K. Phosphorylation of contractile proteins in heart and skeletal muscle. Fed. Proc. 1980, 39(5), 1552–1557. [Google Scholar] [PubMed]
Stull, J.T.; Kamm, K.E.; Vandenboom, R. Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle. Arch. Biochem. Biophys. 2011, 510, 120–128. [Google Scholar] [CrossRef] [PubMed]
Yamaguchi, M.; Kimura, M.; Li, Z.B.; Ohno, T.; Takemori, S.; Hoh, J.F.Y.; Yagi, N. X-ray diffraction analysis of the effects of myosin regulatory light chain phosphorylation and butanedione monoxime on skinned skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 2016, 310, C692–C700. [Google Scholar] [CrossRef]
Heling, L.; Geeves, M.A.; Kad, N.M. MyBP-C: one protein to govern them all. J. Muscle Res. Cell Motil. 2020, 41, 91–101. [Google Scholar] [CrossRef]
Wu, X.; Li, Z.F.; Brooks, R.; Komives, E.A.; Torpey, J.W.; Engvall, E.; Gonias, S.L.; Shelton, G.D. Autoantibodies in canine masticatory muscle myositis recognize a novel myosin binding protein-C family member. J. Immunol. 2007, 179, 4939–4944. [Google Scholar] [CrossRef]
Kang, L.H.; Rughani, A.; Walker, M.L.; Bestak, R.; Hoh, J.F.Y. Expression of masticatory-specific isoforms of myosin heavy-chain, myosin-binding protein-C and tropomyosin in muscle fibers and satellite cell cultures of cat masticatory muscle. J. Histochem. Cytochem. 2010, 58, 623–634. [Google Scholar] [CrossRef]
Li, A.; Nelson, S.R.; Rahmanseresht, S.; Braet, F.; Cornachione, A.S.; Previs, S.B.; O'Leary, T.S.; McNamara, J.W.; Rassier, D.E.; Sadayappan, S.; Previs, M.J.; Warshaw, D.M. Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems. Proc. Natl. Acad. Sci. USA 2019, 116, 21882–21892. [Google Scholar] [CrossRef] [PubMed]
Ponnam, S.; Sevrieva, I.; Sun, Y.B.; Irving, M.; Kampourakis, T. Site-specific phosphorylation of myosin binding protein-C coordinates thin and thick filament activation in cardiac muscle. Proc. Natl. Acad. Sci. USA 2019, 116, 15485–15494. [Google Scholar] [CrossRef] [PubMed]
Gresham, K.S.; Stelzer, J.E. The contributions of cardiac myosin binding protein C and troponin I phosphorylation to β-adrenergic enhancement of in vivo cardiac function. J. Physiol. 2016, 594, 669–686. [Google Scholar] [CrossRef] [PubMed]
Nelson, S.R.; Li, A.; Beck-Previs, S.; Kennedy, G.G.; Warshaw, D.M. Imaging ATP consumption in resting skeletal muscle: one molecule at a time. Biophys. J. 2020, 119, 1050–1055. [Google Scholar] [CrossRef] [PubMed]
Robinett, J.C.; Hanft, L.M.; Geist, J.; Kontrogianni-Konstantopoulos, A.; McDonald, K.S. Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C. J. Gen. Physiol. 2019, 151, 645–659. [Google Scholar] [CrossRef] [PubMed]
Kjellgren, D.; Stål, P.; Larsson, L.; Fürst, D.; Pedrosa-Domellöf, F. , Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles. Invest. Ophthalmol. Visual Sci. 2006, 47, 4188–4193. [Google Scholar] [CrossRef]
Yu, F.; Stål, P.; Thornell, L.E.; Larsson, L. Human single masseter muscle fibers contain unique combinations of myosin and myosin binding protein C isoforms. J. Muscle Res. Cell Motil. 2002, 23, 317–326. [Google Scholar] [CrossRef]
Hoh, J.F.Y. Myosin heavy chains in extraocular muscle fibres: Distribution, regulation and function. Acta Physiol. 2021, 231, e13535. [Google Scholar] [CrossRef]
Hoh, J.F.Y. 'Superfast' or masticatory myosin and the evolution of jaw-closing muscles of vertebrates. J. Exp. Biol. 2002, Pt 15, 2203–2210. [Google Scholar] [CrossRef]
Hoh, J.F. Y, Laryngeal muscle fibre types. Acta Physiol. Scand. 2005, 183, 133–149. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S. Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds. J. Muscle Res. Cell Motil. 1988, 9, 59–72. [Google Scholar]
Kang, L.H.; Hoh, J.F.Y. Regulation of jaw-specific isoforms of myosin-binding protein-C and tropomyosin in regenerating cat temporalis muscle innervated by limb fast and slow motor nerves. J. Histochem. Cytochem. 2010, 58, 989–1004. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S. Expression of superfast myosin in aneural regenerates of cat jaw muscle. Muscle Nerve 1991, 14, 316–325. [Google Scholar] [CrossRef] [PubMed]
Sciote, J.J.; Rowlerson, A.M.; Carlson, D.S. Myosin expression in the jaw-closing muscles of the domestic cat and american opossum. Arch. Oral Biol. 1995, 40, 405–413. [Google Scholar] [CrossRef]
Tsuzuki, S.; Yoshida, S.; Yamamoto, T.; Oka, H. Developmental changes in the electrophysiological properties of neonatal rat oculomotor neurons studied in vitro. Neurosci. Res. 1995, 23, 389–397. [Google Scholar] [CrossRef]
Robinson, D.A. Oculomotor unit behavior in the monkey. J. Neurophysiol. 1970, 33, 393–403. [Google Scholar] [CrossRef] [PubMed]
Carrero-Rojas, G.; Hernández, R.G.; Blumer, R.; de la Cruz, R.R.; Pastor, A.M. MIF versus SIF motoneurons, what are their respective contribution in the oculomotor medial rectus pool? J. Neurosci. 2021, 41, 9782–9793. [Google Scholar] [CrossRef] [PubMed]
Porter, J.D. Commentary: extraocular muscle sparing in muscular dystrophy: a critical evaluation of potential protective mechanisms. Neuromusc.. Disord. 1998, 8, 198–203. [Google Scholar] [CrossRef]
Kaminski, H.J.; Maas, E.; Spiegel, P.; Ruff, R.L. Why are eye muscles frequently involved in myasthenia gravis? Neurology 1990, 40, 1663–1669. [Google Scholar] [CrossRef]
Rhee, H.S.; Hoh, J.F.Y. Immunohistochemical analysis of the effects of cross-innervation of murine thyroarytenoid and sternohyoid muscles. J. Histochem. Cytochem. 2010, 58, 1057–1065. [Google Scholar] [CrossRef]
Rhee, H.S.; Hoh, J.F.Y. Immunohistochemical analysis of myosin heavy chain expression in laryngeal muscles of the rabbit, cat, and baboon. J. Histochem. Cytochem. 2008, 56, 929–950. [Google Scholar] [CrossRef]
Elemans, C.P.; Mead, A.F.; Jakobsen, L.; Ratcliffe, J.M. Superfast muscles set maximum call rate in echolocating bats. Science 2011, 333, 1885–1888. [Google Scholar] [CrossRef]
Revel, J.P. The sarcoplasmic reticulum of the bat cricothyroid muscle. J. Cell Biol. 1962, 12, 571–688. [Google Scholar] [CrossRef]
Reger, J.F. A comparative study on the fine structure of tongue and cricothyroid muscle of the bat, myotis gisescens, as revealed by thin section and freeze-fracture techniques. J. Ultrastruct. Res. 1978, 63, 275–286. [Google Scholar] [CrossRef]
Fonseca, S.; Costa, C.C.; Rêgo, A.P.V.; Velasco, L.C.; Duarte, P.; Roldão, P.; Ramos, H.V.L. laryngeal findings in Duchenne muscular dystrophy. J. Voice 2022, 36, e1–e880. [Google Scholar] [CrossRef]
Marques, M.J.; Ferretti, R.; Vomero, V.U.; Minatel, E.; Neto, H.S. Intrinsic laryngeal muscles are spared from myonecrosis in the mdx mouse model of Duchenne muscular dystrophy. Muscle Nerve 2007, 35, 349–353. [Google Scholar] [CrossRef]
Smythe, G.M. Dystrophic pathology in the intrinsic and extrinsic laryngeal muscles in the mdx mouse. J. Otolaryngol. Head Neck Surg. 2009, 38, 323–336. [Google Scholar] [PubMed]
Thomas, L.B.; Joseph, G.L.; Adkins, T.D.; Andrade, F.H.; Stemple, J.C. Laryngeal muscles are spared in the dystrophin deficient mdx mouse. J. Speech Lang. Hear. Res. 2008, 51, 586–595. [Google Scholar] [CrossRef] [PubMed]
Gilbert, P.W. The origin and development of the extrinsic ocular muscles in the domestic cat. J. Morphol. 1947, 81, 151–193. [Google Scholar] [CrossRef] [PubMed]
Diehl, A.G.; Zareparsi, S.; Qian, M.; Khanna, R.; Angeles, R.; Gage, P.J. Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene dose. Invest. Ophthalmol. Visual Sci. 2006, 47, 1785–1793. [Google Scholar] [CrossRef] [PubMed]
Tajbakhsh, S.; Rocancourt, D.; Cossu, G.; Buckingham, M. Redefining the genetic hierarchies controlling skeletal myogenesis - pax-3 and myf-5 act upstream of myod. Cell 1997, 89, 127–138. [Google Scholar] [CrossRef]
Chang, C.N.; Kioussi, C. Location, Location, Location: Signals in Muscle Specification. J. Dev. Biol. 2018, 6. [Google Scholar] [CrossRef]
Zhou, Y.; Cheng, G.; Dieter, L.; Hjalt, T.A.; Andrade, F.H.; Stahl, J.S.; Kaminski, H.J. An altered phenotype in a conditional knockout of Pitx2 in extraocular muscle. Invest. Ophthalmol. Visual Sci. 2009, 50, 4531–4541. [Google Scholar] [CrossRef] [PubMed]
Zhou, Y.; Liu, D.; Kaminski, H.J. Pitx2 regulates myosin heavy chain isoform expression and multi-innervation in extraocular muscle. J. Physiol. 2011, Pt 18, 4601–4614. [Google Scholar] [CrossRef]
Mascarello, F.; Rowlerson, A.M. Myosin isoform transitions during development of extraocular and masticatory muscles in the fetal rat. Anat. Embryol. (Berl) 1992, 185, 143–153. [Google Scholar] [CrossRef]
Brueckner, J.K.; Itkis, O.; Porter, J.D. Spatial and temporal patterns of myosin heavy chain expression in developing rat extraocular muscle. J. Muscle Res. Cell Motil. 1996, 17, 297–312. [Google Scholar] [CrossRef]
Brueckner, J.K.; Porter, J.D. Visual system maldevelopment disrupts extraocular muscle-specific myosin expression. J. Appl. Physiol. 1998 85, 584–592. [CrossRef]
Brueckner, J.K.; Ashby, L.P.; Prichard, J.R.; Porter, J.D. Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns. Cell Tissue Res. 1999, 295, 477–484. [Google Scholar] [CrossRef]
Zhou, Y.; Liu, D.; Kaminski, H.J. Myosin heavy chain expression in mouse extraocular muscle: more complex than expected. Invest. Ophthalmol. Visual Sci. 2010, 51, 6355–6363. [Google Scholar] [CrossRef] [PubMed]
Rubinstein, N.A.; Porter, J.D.; Hoh, J.F.Y. The development of longitudinal variation of Myosin isoforms in the orbital fibers of extraocular muscles of rats. Invest. Ophthalmol. Visual Sci. 2004, 45, 3067–3072. [Google Scholar] [CrossRef] [PubMed]
Moncman, C.L.; Andrade, M.E.; Andrade, F.H. Postnatal changes in the developing rat extraocular muscles. Invest. Ophthalmol. Visual Sci. 2011, 52, 3962–3969. [Google Scholar] [CrossRef]
d’Albis, A.; Butler-Browne, G. The hormonal control of myosin isoform expression in skeletal muscle of mammals: a review. Basic Appl. Myol. 1993, 3, 7–16. [Google Scholar]
Hoh, J.F.Y. Developmental, physiologic and phylogenetic perspectives on the expression and regulation of myosin heavy chains in mammalian skeletal muscles. J. Comp. Physiol. B 2023, 193, 355–382. [Google Scholar] [CrossRef]
Pitts, E.V.; Potluri, S.; Hess, D.M.; Balice-Gordon, R.J. Neurotrophin and Trk-mediated signaling in the neuromuscular system. Int. Anesthesiol. Clin. 2006, 44, 21–76. [Google Scholar] [CrossRef]
Morcuende, S.; Benítez-Temiño, B.; Pecero, M.L.; Pastor, A.M.; de la Cruz, R.R. Abducens internuclear neurons depend on their target motoneurons for survival during early postnatal development. Exp. Neurol. 2005, 195, 244–256. [Google Scholar] [CrossRef] [PubMed]
Morcuende, S.; Muñoz-Hernández, R.; Benítez-Temiño, B.; Pastor, A.M.; de la Cruz, R.R. Neuroprotective effects of NGF, BDNF, NT-3 and GDNF on axotomized extraocular motoneurons in neonatal rats. Neuroscience 2013, 250, 31–48. [Google Scholar] [CrossRef] [PubMed]
Carrero-Rojas, G.; Benítez-Temiño, B.; Pastor, A.M.; Davis López de Carrizosa, M.A. Muscle progenitors derived from extraocular muscles express higher levels of neurotrophins and their receptors than other cranial and limb muscles. Cell 2020, 9. [Google Scholar] [CrossRef]
Buttner-Ennever, J.A.; Horn, A.K. Anatomical substrates of oculomotor control. Cur. Opin. Neurobiol. 1997, 7, 872–879. [Google Scholar] [CrossRef]
Sparks, D.L. The brainstem control of saccadic eye movements. Nat. Rev. Neurosci. 2002, 3, 952–964. [Google Scholar] [CrossRef]
Büttner-Ennever, J.A. Anatomy of the oculomotor system. Neuroophthalmology 2007, 40, 1–14. [Google Scholar]
Spencer, R.F.; Porter, J.D. Biological organization of the extraocular muscles. Prog. Brain Res. 2006, 151, 43–80. [Google Scholar]
Wong, A.M. Listing's law: clinical significance and implications for neural control. Surv. Ophthalmol. 2004, 49, 563–575. [Google Scholar] [CrossRef]
Wieczorek, D.F.; Periasamy, M.; Butler-Browne, G.S.; Whalen, R.G.; Nadal-Ginard, B. Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature. J. Cell Biol. 1985, 101, 618–629. [Google Scholar] [CrossRef]
Jacoby, J.; Ko, K.; Weiss, C.; Rushbrook, J.I. Systematic variation in myosin expression along extraocular muscle fibres of the adult rat. J. Muscle Res. Cell Motil. 1989, 11, 25–40. [Google Scholar] [CrossRef]
Rubinstein, N.A.; Hoh, J.F.Y. The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types. Invest. Ophthalmol. Visual Sci. 2000 41, 3391–3398.
Briggs, M.M.; Schachat, F. The superfast extraocular myosin (MYH13) is localized to the innervation zone in both the global and orbital layers of rabbit extraocular muscle. J. Exp. Biol. 2002, Pt 20, 3133–3142. [Google Scholar] [CrossRef]
Lucas, C.A.; Hoh, J.F.Y. Distribution of developmental myosin heavy chains in adult rabbit extraocular muscle: identification of a novel embryonic isoform absent in fetal limb. Invest. Ophthalmol. Visual Sci. 2003, 44, 2450–2456. [Google Scholar] [CrossRef]
Lucas, C.A.; Rhee, H.S.M.; Hoh, J.F.Y. Changes in myosin heavy chain isoforms along the length of orbital fibers in rabbit extraocular muscle. Invest. Ophthalmol. Visual Sci. 2018, 59, 1178–1190. [Google Scholar] [CrossRef] [PubMed]
Fraterman, S.; Zeiger, U.; Khurana, T.S.; Wilm, M.; Rubinstein, N.A. Quantitative proteomics profiling of sarcomere associated proteins in limb and extraocular muscle allotypes. Mol. Cell. Proteomics 2007, 6, 728–737. [Google Scholar] [CrossRef] [PubMed]
Porter, J.D.; Khanna, S.; Kaminski, H.J.; Rao, J.S.; Merriam, A.P.; Richmonds, C.R.; Leahy, P.; Li, J.; Andrade, F.H. Extraocular muscle is defined by a fundamentally distinct gene expression profile. Proc. Natl. Acad. Sci. USA 2001, 98, 12062–12067. [Google Scholar] [CrossRef] [PubMed]
Fischer, M.D.; Budak, M.T.; Bakay, M.; Gorospe, J.R.; Kjellgren, D.; Pedrosa-Domellof, F.; Hoffman, E.P.; Khurana, T.S. Definition of the unique human extraocular muscle allotype by expression profiling. Physiol. Genomics 2005, 22, 283–291. [Google Scholar] [CrossRef] [PubMed]
Ketterer, C.; Zeiger, U.; Budak, M.T.; Rubinstein, N.A.; Khurana, T.S. Identification of the neuromuscular junction transcriptome of extraocular muscle by laser capture microdissection. Invest. Ophthalmol. Visual Sci. 2010, 51, 4589–4599. [Google Scholar] [CrossRef] [PubMed]
Kato, T. Uber histologische Untersuchungen der Augenmuskelin von Menschen und Saugetieren. Okajimas Folia Anat. Jpn. 1938, 16, 131–145. [Google Scholar] [CrossRef]
Spencer, R.F.; Porter, J.D. Structural organization of the extraocular muscles. In Neuroanatomy of the oculomotor system; Buttner-Ennever, Ed. Elsevier Science Publisher: New York, 1988; pp. 33–79. [Google Scholar]
Jacoby, J.; Chiarandini, D.J.; Stefani, E. Electrical properties and innervation of fibers in the orbital layer of rat extraocular muscles. J. Neurophysiol. 1989, 61, 116–125. [Google Scholar] [CrossRef] [PubMed]
Lennerstrand, G. Electrical activity and isometric tension in motor units of the cat's inferior oblique muscle. Acta Physiol. Scand. 1974, 91, 458–474. [Google Scholar] [CrossRef]
Ruskell, G.L. The fine structure of innervated myotendinous cylinders in extraocular muscles of rhesus monkeys. J. Neurocytol. 1978, 7, 693–708. [Google Scholar] [CrossRef]
Blumer, R.; Maurer-Gesek, B.; Gesslbauer, B.; Blumer, M.; Pechriggl, E.; Davis-Lopez de Carrizosa, M.A.; Horn, A.K.; May, P.J.; Streicher, J.; de la Cruz, R.R.; Pastor, A.M. palisade endings are a constant feature in the extraocular muscles of frontal-eyed, but not lateral-eyed, animals. Invest. Ophthalmol. Visual Sci. 2016, 57, 320–331. [Google Scholar] [CrossRef]
Zimmermann, L.; May, P.J.; Pastor, A.M.; Streicher, J.; Blumer, R. Evidence that the extraocular motor nuclei innervate monkey palisade endings. Neurosci Lett. 2011, 489, 89–93. [Google Scholar] [CrossRef]
Zimmermann, L.; Morado-Díaz, C.J.; Davis-López de Carrizosa, M.A.; de la Cruz, R.R.; May, P.J.; Streicher, J.; Pastor, Á. M.; Blumer, R. Axons giving rise to the palisade endings of feline extraocular muscles display motor features. J. Neurosci. 2013, 33, 2784–2793. [Google Scholar] [CrossRef] [PubMed]
Lienbacher, K.; Mustari, M.; Hess, B.; Büttner-Ennever, J.; Horn, A.K. Is there any sense in the Palisade endings of eye muscles? Ann. N. Y. Acad. Sci. 2011, 1233, 1–7. [Google Scholar] [CrossRef] [PubMed]
Blumer, R.; Wasicky, R.; Hotzenecker, W.; Lukas, J.R. Presence and structure of innervated myotendinous cylinders in rabbit extraocular muscle. Exp. Eye Res. 2001, 73, 787–796. [Google Scholar] [CrossRef] [PubMed]
Konakci, K.Z.; Streicher, J.; Hoetzenecker, W.; Blumer, M.J.; Lukas, J.R.; Blumer, R. Molecular characteristics suggest an effector function of palisade endings in extraocular muscles. Invest. Ophthalmol. Visual Sci. 2005, 46, 155–165. [Google Scholar] [CrossRef] [PubMed]
Budak, M.T.; Bogdanovich, S.; Wiesen, M.H.; Lozynska, O.; Khurana, T.S.; Rubinstein, N.A. Layer-specific differences of gene expression in extraocular muscles identified by laser-capture microscopy. Physiol. Genomics 2004, 20, 55–65. [Google Scholar] [CrossRef] [PubMed]
Khanna, S.; Cheng, G.; Gong, B.; Mustari, M.J.; Porter, J.D. Genome-wide transcriptional profiles are consistent with functional specialization of the extraocular muscle layers. Invest. Ophthalmol. Visual Sci. 2004, 45, 3055–3066. [Google Scholar] [CrossRef] [PubMed]
Demer, J.L.; Miller, J.M.; Poukens, V.; Vinters, H.V.; Glasgow, B.J. Evidence for fibromuscular pulleys of the recti extraocular muscles. Invest. Ophthalmol. Vis. Sci. 1995, 36, 1125–1136. [Google Scholar] [PubMed]
Davidowitz, J.; Philips, G.; Breinin, G.M. Organization of the orbital surface layer in rabbit superior rectus. Invest. Ophthalmol. Visual Sci. 1977, 16, 711–729. [Google Scholar]
Ruskell, G.L.; Kjellevold Haugen, I.B.; Bruenech, J.R.; van der Werf, F. Double insertions of extraocular rectus muscles in humans and the pulley theory. J. Anat. 2005, 206, 295–306. [Google Scholar] [CrossRef]
Scott, A.B.; Collins, C.C. Division of labor in human extraocular muscle. Arch. Ophthalmol. 1973, 90, 319–322. [Google Scholar] [CrossRef]
Collins, C.C.; O'Meara, D.; Scott, A.B. Muscle tension during unrestrained human eye movements. J. Physiol. 1975, 245, 351–369. [Google Scholar] [CrossRef]
Barmack, N.H. Laminar organization of the extraocular muscles of the rabbit. Exp. Neurol. 1978, 59, 304–321. [Google Scholar] [CrossRef]
Demer, J.L.; Oh, S.Y.; Poukens, V. Evidence for active control of rectus extraocular muscle pulleys. Invest. Ophthalmol. Visual Sci. 2000, 41, 1280–1290. [Google Scholar]
Miller, J.M. Understanding and misunderstanding extraocular muscle pulleys. J. Vision 2007, 7, 10–1. [Google Scholar] [CrossRef] [PubMed]
Buttner-Ennever, J.A.; Horn, A.K.; Scherberger, H.; D'Ascanio, P. Motoneurons of twitch and nontwitch extraocular muscle fibers in the abducens, trochlear, and oculomotor nuclei of monkeys. J. Comp. Neurol. 2001, 438, 318–335. [Google Scholar] [CrossRef] [PubMed]
Lienbacher, K.; Mustari, M.; Ying, H.S.; Buttner-Ennever, J.A.; Horn, A.K. Do palisade endings in extraocular muscles arise from neurons in the motor nuclei? Invest. Ophthalmol. Visual Sci. 2011, 52, 2510–2519. [Google Scholar] [CrossRef]
Hernández, R.G.; Calvo, P.M.; Blumer, R.; de la Cruz, R.R.; Pastor, A.M. Functional diversity of motoneurons in the oculomotor system. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 3837–3846. [Google Scholar] [CrossRef] [PubMed]
Blumer, R.; Streicher, J.; Davis-López de Carrizosa, M.A.; de la Cruz, R.R.; Pastor, A.M. Palisade endings of extraocular muscles develop postnatally following different time courses. Invest. Ophthalmol. Vis. Sci. 2017, 58, 5105–5121. [Google Scholar] [CrossRef] [PubMed]
Davis-Lopez de Carrizosa, M.A.; Morado-Diaz, C.J.; Miller, J.M.; de la Cruz, R.R.; Pastor, A.M. Dual encoding of muscle tension and eye position by abducens motoneurons. J. Neurosci. 2011, 31, 2271–2279. [Google Scholar] [CrossRef]
Davis-Lopez de Carrizosa, M.A.; Morado-Diaz, C.J.; Tena, J.J.; Benitez-Temino, B.; Pecero, M.L.; Morcuende, S.R.; de la Cruz, R.R.; Pastor, A.M. Complementary actions of BDNF and neurotrophin-3 on the firing patterns and synaptic composition of motoneurons. J. Neurosci. 2009, 29, 575–587. [Google Scholar] [CrossRef]
Benítez-Temiño, B.; Davis-López de Carrizosa, M.A.; Morcuende, S.; Matarredona, E.R.; de la Cruz, R.R.; Pastor, A.M. Functional diversity of neurotrophin actions on the oculomotor system. Int. J. Mol. Sci. 2016, 17. [Google Scholar] [CrossRef]
Hernández, R.G.; Silva-Hucha, S.; Morcuende, S.; de la Cruz, R.R.; Pastor, A.M.; Benítez-Temiño, B. extraocular motor system exhibits a higher expression of neurotrophins when compared with other brainstem motor systems. Front. Neurosci. 2017, 11, 399. [Google Scholar] [CrossRef]
Davis-Lopez de Carrizosa, M.A.; Morado-Diaz, C.J.; Morcuende, S.; de la Cruz, R.R.; Pastor, A.M. Nerve growth factor regulates the firing patterns and synaptic composition of motoneurons. J. Neurosci. 2010, 30, 8308–8319. [Google Scholar] [CrossRef]
Pachter, B.R.; Davidowitz, J.; Breinin, G.M. Light and electron microscopic serial analysis of mouse extraocular muscle: morphology, innervation and topographical organization of component fiber populations. Tissue Cell 1976, 8, 547–560. [Google Scholar] [CrossRef]
Pachter, B.R. Rat extraocular muscle. 1. Three dimensional cytoarchitecture, component fibre populations and innervation. J. Anat. 1983, 137, 143–159. [Google Scholar]
Davidowitz, J.; Philips, G.; Breinin, G.M. Variation of mitochondrial volume fraction along multiply innervated fibers in rabbit extraocular muscle. Tissue Cell 1980, 12, 449–457. [Google Scholar] [CrossRef]
Pachter, B.R. Rat extraocular muscle. 3. Histochemical variability along the length of multiply-innervated fibers of the orbital surface layer. Histochemistry 1984, 80, 535–538. [Google Scholar] [CrossRef] [PubMed]
Bicer, S.; Reiser, P.J. Myosin light chain 1 isoforms in slow fibers from global and orbital layers of canine rectus muscles. Invest. Ophthalmol. Visual Sci. 2004, 45, 138–143. [Google Scholar] [CrossRef] [PubMed]
Hill, A.V. The abrupt transition from rest to activity in muscle. Proc. Roy. Soc. B 1949, 136, 399–420. [Google Scholar]
Kranjc, B.S.; Sketelj, J.; D'Albis, A.; Erzen, I. Long-term changes in myosin heavy chain composition after botulinum toxin a injection into rat medial rectus muscle. Invest. Ophthalmol. Visual Sci. 2001, 42, 3158–3164. [Google Scholar]
Feng, T.P.; Wu, W.Y.; Yang, F.Y. Selective reinnervation of a 'slow' or 'fast' muscle by its original motor supply during regeneration of mixed nerve. Scientia Sin. 1965, 14, 1717–1720. [Google Scholar]
Hoh, J.F.Y. , Selective reinnervation of fast-twitch and slow-graded muscle fibers in the toad. Exp. Neurol. 1971, 30, 263–276. [Google Scholar] [CrossRef] [PubMed]
Hennig, R.; Lomo, T. Firing patterns of motor units in normal rats. Nature 1985, 314, 164–166. [Google Scholar] [CrossRef] [PubMed]
Ausoni, S.; Gorza, L.; Schiaffino, S.; Gundersen, K.; Lomo, T. Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles. J. Neurosci. 1990, 10, 153–160. [Google Scholar] [CrossRef]
Harrison, A.R.; Lee, M.S.; McLoon, L.K. Effects of elevated thyroid hormone on adult rabbit extraocular muscles. Invest. Ophthalmol. Visual Sci. 2010, 51, 183–191. [Google Scholar] [CrossRef] [PubMed]
Tzahor, E. Heart and craniofacial muscle development: a new developmental theme of distinct myogenic fields. Dev. Biol. 2009, 327, 273–279. [Google Scholar] [CrossRef]
Shih, H.P.; Gross, M.K.; Kioussi, C. Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch. Proc. Natl. Acad. Sci.USA 2007, 104, 5907–5912. [Google Scholar] [CrossRef]
Kelly, R.G.; Jerome-Majewska, L.A.; Papaioannou, V.E. The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Hum. Mol. Genet. 2004, 13, 2829–2840. [Google Scholar] [CrossRef]
Lu, J.R.; Bassel-Duby, R.; Hawkins, A.; Chang, P.; Valdez, R.; Wu, H.; Gan, L.; Shelton, J.M.; Richardson, J.A.; Olson, E.N. Control of facial muscle development by MyoR and capsulin. Science 2002, 298, 2378–2381. [Google Scholar] [CrossRef] [PubMed]
Nathan, E.; Monovich, A.; Tirosh-Finkel, L.; Harrelson, Z.; Rousso, T.; Rinon, A.; Harel, I.; Evans, S.M.; Tzahor, E. The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development. Development 2008, 135, 647–657. [Google Scholar] [CrossRef]
Harel, I.; Maezawa, Y.; Avraham, R.; Rinon, A.; Ma, H.Y.; Cross, J.W.; Leviatan, N.; Hegesh, J.; Roy, A.; Jacob-Hirsch, J.; Rechavi, G.; Carvajal, J.; Tole, S.; Kioussi, C.; Quaggin, S.; Tzahor, E. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis. Proc. Natl. Acad. Sci.USA 2012, 109, 18839–18844. [Google Scholar] [CrossRef]
Bubb, W.J.; Sims, M.H. Fiber type composition of rostral and caudal portions of the digastric muscle in the dog. Am. J. Vet Res. 1986, 47, 1834–1842. [Google Scholar]
Hoh, J.F.Y.; Lim, J.H.Y.; Kang, L.D.H.; Lucas, C.A. Expression of superfast myosin in the jaw-closing muscles of Crocodylus porosus. In Crocodilian Biology and Evolution, Grigg, G.C.; Seebacher, F., Ed.; Franklin, C.E. Eds. Surrey Beatty & Sons: Chipping Norton, 2001. [Google Scholar]
Rowlerson, A.; Mascarello, F.; Veggetti, A.; Carpene, E. The fibre-type composition of the first branchial arch muscles in Carnivora and Primates. J. Muscle Res. Cell Motil. 1983, 4, 443–472. [Google Scholar] [CrossRef]
Collins, J.H. Myosin light chains and troponin-c - structural and evolutionary relationships revealed by amino acid sequence comparisons. J. Muscle Res. Cell Motil. 1991, 12, 3–25. [Google Scholar] [CrossRef]
Rowlerson, A.; Heizmann, C.W.; Jenny, E. Type-specific proteins of single IIM fibres from cat muscle. Biochem. Biophys. Res. Commun. 1983, 113, 519–525. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S.; Walker, M.L.; Kang, L.H.D.; Everett, A.W. Slow myosin heavy chains in cat jaw and limb muscles are phenotypically distinct: expression of jaw-specific slow myosin phenotype in regenerated and chronically stimulated jaw muscles. Basic Appl. Myol. 1991, 1, 285–294. [Google Scholar]
Shelton, G.D.; Cardinet, G.H. 3rd; Bandman, E. Expression of fiber type specific proteins during ontogeny of canine temporalis muscle. Muscle Nerve 1988, 11, 124–132. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S. Immunocytochemical analysis of the perinatal development of cat masseter muscle using anti-myosin antibodies. J. Muscle Res. Cell Motil. 1989, 10, 312–325. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S.; Chow, C.; Hale, P.T.; Fitzsimons, R.B. Immunocytochemical and electrophoretic analyses of changes in myosin gene expression in cat posterior temporalis muscle during postnatal development. J. Muscle Res. Cell Motil. 1988, 9, 48–58. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Hughes, S.; Hale, P.T.; Fitzsimons, R.B. Immunocytochemical and electrophoretic analyses of changes in myosin gene expression in cat limb fast and slow muscles during postnatal development. J. Muscle Res. Cell Motil. 1988, 9, 30–47. [Google Scholar] [CrossRef] [PubMed]
Zhong, W.W.; Withers, K.W.; Hoh, J.F.Y. Effects of hypothyroidism on myosin heavy chain composition and fibre types of fast skeletal muscles in a small marsupial, Antechinus flavipes. J Comp. Physiol. B 2010, 180, 531–544. [Google Scholar] [CrossRef] [PubMed]
Izumo, S.; Nadal-Ginard, B.; Mahdavi, V. All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science 1986, 231, 597–600. [Google Scholar] [CrossRef] [PubMed]
Mahdavi, V.; Izumo, S.; Nadal-Ginard, B. Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family. Circ. Res. 1987, 60, 804–814. [Google Scholar] [CrossRef] [PubMed]
Taylor, A.; Cody, F.W.J.; Bosley, M.A. Histochemical and mechanical properties of the jaw muscles of the cat. Exp. Neurol. 1973, 38, 99–109. [Google Scholar] [CrossRef] [PubMed]
Toniolo, L.; Cancellara, P.; Maccatrozzo, L.; Patruno, M.; Mascarello, F.; Reggiani, C. Masticatory myosin unveiled: first determination of contractile parameters of muscle fibers from carnivore jaw muscles. Am. J. Physiol. Cell Physiol. 2008, 295, C1535–42. [Google Scholar] [CrossRef]
Kato, C.; Saeki, Y.; Yanagisawa, K. Ca²⁺ sensitivities and transient tension responses to step-length stretches in feline mechanically-stripped single-fibre jaw-muscle preparations. Arch. Oral Biol. 1985, 30, 429–432. [Google Scholar] [CrossRef] [PubMed]
Close, R.; Hoh, J.F.Y. The after-effects of repetitive stimulation on the isometric twitch contraction of rat fast skeletal muscle. J. Physiol. 1968, 197, 461–477. [Google Scholar] [CrossRef]
Saeki, Y.; Kato, C.; Satomi, M.; Yanagisawa, K. ATPase activity and tension development in mechanically-skinned feline jaw muscle. Arch. Oral Biol. 1987, 32, 207–210. [Google Scholar] [CrossRef]
Katz, B. The relation between force and speed in muscular contraction. J. Physiol. 1939, 96, 45–64. [Google Scholar] [CrossRef]
Linari, M.; Bottinelli, R.; Pellegrino, M.A.; Reconditi, M.; Reggiani, C.; Lombardi, V. The mechanism of the force response to stretch in human skinned muscle fibres with different myosin isoforms. J. Physiol. 2004, Pt 2, 335–352. [Google Scholar] [CrossRef]
Rossmanith, G.H.; Tjokorda, O.B. Relationships between isometric and isotonic mechanical parameters and cross-bridge kinetics. Clin. Exp. Pharmacol. Physiol 1998, 25, 522–535. [Google Scholar] [CrossRef] [PubMed]
Kang, L.H.; Hoh, J.F.Y. Chronic low-frequency stimulation transforms cat masticatory muscle fibers into jaw-slow fibers. J. Histochem. Cytochem. 2011, 59, 849–863. [Google Scholar] [CrossRef] [PubMed]
Chin, E.R.; Olson, E.N.; Richardson, J.A.; Yang, Q.; Humphries, C.; Shelton, J.M.; Wu, H.; Zhu, W.; Bassel-Duby, R.; Williams, R.S. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998, 12, 2499–2509. [Google Scholar] [CrossRef]
Naya, F.J.; Mercer, B.; Shelton, J.; Richardson, J.A.; Williams, R.S.; Olson, E.N. Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J. Biol. Chem. 2000, 275, 4545–4548. [Google Scholar] [CrossRef]
McCullagh, K.J.; Calabria, E.; Pallafacchina, G.; Ciciliot, S.; Serrano, A.L.; Argentini, C.; Kalhovde, J.M.; Lomo, T.; Schiaffino, S. NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching. Proc. Natl. Acad. Sci. USA. 2004, 101, 10590–10595. [Google Scholar] [CrossRef]
Calabria, E.; Ciciliot, S.; Moretti, I.; Garcia, M.; Picard, A.; Dyar, K.A.; Pallafacchina, G.; Tothova, J.; Schiaffino, S.; Murgia, M. NFAT isoforms control activity-dependent muscle fiber type specification. Proc. Natl. Acad. Sci. USA 2009, 106, 13335–13340. [Google Scholar] [CrossRef] [PubMed]
Dos Santos, M.; Shah, A.M.; Zhang, Y.; Bezprozvannaya, S.; Chen, K.; Xu, L.; Lin, W.; McAnally, J.R.; Bassel-Duby, R.; Liu, N.; Olson, E.N. Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution. Nature Commun. 2023, 14, 4333. [Google Scholar] [CrossRef]
Sadaki, S.; Fujita, R.; Hayashi, T.; Nakamura, A.; Okamura, Y.; Fuseya, S.; Hamada, M.; Warabi, E.; Kuno, A.; Ishii, A.; Muratani, M.; Okada, R.; Shiba, D.; Kudo, T.; Takeda, S.; Takahashi, S. Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination. Cell Reports 2023, 42, 112289. [Google Scholar] [CrossRef] [PubMed]
Sciote, J.J.; Rowlerson, A. Skeletal fiber types and spindle distribution in limb and jaw muscles of the adult and neonatal opossum, monodelphis domestica. Anat. Rec. 1998, 251, 548–562. [Google Scholar] [CrossRef]
Hoh, J.F.Y.; Kang, L.H.; Sieber, L.G.; Lim, J.H.; Zhong, W.W. Myosin isoforms and fibre types in jaw-closing muscles of Australian marsupials. J. Comp. Physiol. B 2006, 176, 685–695. [Google Scholar] [CrossRef] [PubMed]
Kang, L.H.D.; Hughes, S.; Pettigrew, J.D.; Hoh, J.F.Y. Jaw-specific myosin heavy chain gene expression in sheep, dog, monkey, flying fox and microbat jaw-closing muscles. Basic Appl. Myol. 1994, 4, 381–392. [Google Scholar]
Reiser, P.J.; Bicer, S.; Chen, Q.; Zhu, L.; Quan, N. Masticatory (‘superfast') myosin heavy chain and embryonic/atrial myosin light chain 1 in rodent jaw-closing muscles. J. Exp. Biol. 2009, Pt 16, 2511–2519. [Google Scholar] [CrossRef]
Wall, C.E.; Briggs, M.M.; Huq, E.; Hylander, W.L.; Schachat, F. Regional variation in IIM myosin heavy chain expression in the temporalis muscle of female and male baboons (Papio anubis). Arch. Oral Biol. 2013, 58, 435–443. [Google Scholar] [CrossRef] [PubMed]
Bicer, S.; Patel, R.J.; Williams, J.B.; Reiser, P.J. Patterns of tropomyosin and troponin-T isoform expression in jaw-closing muscles of mammals and reptiles that express masticatory myosin. J. Exp. Biol. 2011, Pt 7, 1077–1085. [Google Scholar] [CrossRef]
Wall, C.E.; Holmes, M.; Soderblom, E.J.; Taylor, A.B. Proteomics and immunohistochemistry identify the expression of alpha-cardiac myosin heavy chain in the jaw-closing muscles of sooty mangabeys (order Primates). Arch. Oral Biol. 2018, 91, 103–108. [Google Scholar] [CrossRef] [PubMed]
Bredman, J.J.; Wessels, A.; Weijs, W.A.; Korfage, J.A.M.; Soffers, C.A.S.; Moorman, A.F.M. Demonstration of cardiac-specific myosin heavy chain in masticatory muscles of human and rabbit. Histochem. J. 1991, 23, 160–170. [Google Scholar] [CrossRef] [PubMed]
Korfage, J.A.; Van Eijden, T.M. Myosin isoform composition of the human medial and lateral pterygoid muscles. J. Dent. Res. 2000, 79, 1618–1625. [Google Scholar] [CrossRef] [PubMed]
Osterlund, C.; Lindström, M.; Thornell, L.E.; Eriksson, P.O. Remarkable heterogeneity in myosin heavy-chain composition of the human young masseter compared with young biceps brachii. Histochem. Cell Biol. 2012, 138, 669–682. [Google Scholar] [CrossRef] [PubMed]
Stedman, H.H.; Kozyak, B.W.; Nelson, A.; Thesier, D.M.; Su, L.T.; Low, D.W.; Bridges, C.R.; Shrager, J.B.; Minugh-Purvis, N.; Mitchell, M.A. Myosin gene mutation correlates with anatomical changes in the human lineage. Nature 2004, 428, 415–418. [Google Scholar] [CrossRef]
Stal, P.; Eriksson, P.O.; Schiaffino, S.; Butler-Browne, G.S.; Thornell, L.E. Differences in myosin composition between human oro-facial, masticatory and limb muscles: Enzyme-, immunohisto- and biochemical studies. J. Muscle Res. Cell Motil. 1994, 15, 517–534. [Google Scholar] [CrossRef]
Suzuki, A. A comparative histochemical study of the masseter muscle of the cattle, sheep, swine, dog, guinea pig and rat. Histochemistry 1977, 51, 121–131. [Google Scholar] [CrossRef]
Mascarello, F.; Aureli, G.; Vegetti, A. Muscoli masticatori: determinazione istochimica dei tipi di fibre muscolari. Quad. Anat. Prat. 1979, 35, 193–213. [Google Scholar]
Dawson, T.J. Kangaroos - Biology of the Largest Marsupials; University of New South Wales Press: Sydney, 1995. [Google Scholar]
Sfondrini, G.; Reggiani, C.; Gandini, P.; Bovenzi, R.; Pellegrino, M.A. Adaptations of masticatory muscles to a hyperpropulsive appliance in the rat. Am. J. Orthod. Dentofacial Orthop. 1996, 110, 612–617. [Google Scholar] [CrossRef] [PubMed]
Lindman, R.; Eriksson, P.O.; Thornell, L.E. Histochemical enzyme profile of the masseter, temporal and lateral pterygoid muscles of the European hedgehog (Erinaceus europeaus). Arch. Oral Biol. 1986, 31, 51–55. [Google Scholar] [CrossRef]
Lyons, G.E.; Kelly, A.M.; Rubinstein, N.A. Testosterone-induced changes in contractile protein isoforms in the sexually dimorphic temporalis muscle of the guinea pig. J. Biol. Chem. 1986, 261, 13278–13284. [Google Scholar] [CrossRef]
English, A.W.; Eason, J.; Schwartz, G.; Shirley, A.; Carrasco, D.I. Sexual dimorphism in the rabbit masseter muscle: myosin heavy chain composition of neuromuscular compartments. Cells Tissues Organs 1999, 164, 179–191. [Google Scholar] [CrossRef] [PubMed]
Hall, S. The diets of two coexisting species of Antechinus (Marsupialian: Dasyuridae). Aust. Wildlife Res. 1980, 7, 365–378. [Google Scholar] [CrossRef]
Morton, S.R.; Denny, M.J.S.; Read, D.G. Habitat preferences and diets of sympatric Sminthopsis crassicaudata and S. macroura. (Marsupialia: Dasyuridae). Aust. Mammal. 1983, 6, 29–34. [Google Scholar]
Hume, I.D. Marsupial Nutrition; Cambridge University Press, 1999. [Google Scholar]
Thomson, J.A.; Qowen, W.H. A field study of the Australian ringtail possum Pseudocheirus peregrinus (Marsupialia: Phalangeridae). Ecol. Monogr. 1964, 34, 27–52. [Google Scholar] [CrossRef]
Hoh, J.F.Y. Kim, Y.; Sieber, L.G.; Zhong, W.W.; Lucas, C.A. Jaw-closing muscles of kangaroos express alpha-cardiac myosin heavy chain. J. Muscle Res. Cell Motil. 2000, 21, 673–680. [Google Scholar] [CrossRef]
Kiliaridis, S.; Engström, C.; Thilander, B. Histochemical analysis of masticatory muscle in the growing rat after prolonged alteration in the consistency of the diet. Arch. Oral Biol. 1988, 33, 187–193. [Google Scholar] [CrossRef]
Kawai, N.; Sano, R.; Korfage, J.A.; Nakamura, S.; Kinouchi, N.; Kawakami, E.; Tanne, K.; Langenbach, G.E.; Tanaka, E. Adaptation of rat jaw muscle fibers in postnatal development with a different food consistency: an immunohistochemical and electromyographic study. J. Anat. 2010, 216, 717–723. [Google Scholar] [CrossRef]
Saito, T.; Ohnuki, Y.; Yamane, A.; Saeki, Y. Effects of diet consistency on the myosin heavy chain mRNAs of rat masseter muscle during postnatal development. Arch. Oral Biol. 2002, 47, 109–115. [Google Scholar] [CrossRef]
Kitagawa, Y.; Mitera, K.; Ogasawara, T.; Nojyo, Y.; Miyauchi, K.; Sano, K. Alterations in enzyme histochemical characteristics of the masseter muscle caused by long-term soft diet in growing rabbits. Oral Dis. 2004, 10, 271–276. [Google Scholar] [CrossRef] [PubMed]
Vreeke, M.; Langenbach, G.E.; Korfage, J.A.; Zentner, A.; Grünheid, T. The masticatory system under varying functional load. Part 1: Structural adaptation of rabbit jaw muscles to reduced masticatory load. Eur. J. Orthod. 2011, 33, 359–364. [Google Scholar] [CrossRef] [PubMed]
Ohnuki, Y.; Saeki, Y.; Yamane, A.; Yanagisawa, K. Quantitative changes in the mRNA for contractile proteins and metabolic enzymes in masseter muscle of bite-opened rats. Arch. Oral Biol. 2000, 45, 1025–1032. [Google Scholar] [CrossRef] [PubMed]
Ohnuki, Y.; Kawai, N.; Tanaka, E.; Langenbach, G.E.; Tanne, K.; Saeki, Y. Effects of increased occlusal vertical dimension on daily activity and myosin heavy chain composition in rat jaw muscle. Arch. Oral Biol. 2009, 54, 783–789. [Google Scholar] [CrossRef] [PubMed]
Arai, C.; Ohnuki, Y.; Umeki, D.; Saeki, Y. Effects of bite-opening and cyclosporin A on the mRNA levels of myosin heavy chain and the muscle mass in rat masseter. Jap. J. Physiol. 2005, 55, 173–179. [Google Scholar] [CrossRef] [PubMed]
Kawasaki, K.; Saeki, Y.; Ohnuki, Y. Effect of an increase in occlusal vertical dimension on the rate of cyclic actin-myosin interaction in guinea-pig masseter muscle. Arch. Oral Biol. 1997, 42, 505–512. [Google Scholar] [CrossRef] [PubMed]
Eason, J.M.; Schwartz, G.A.; Pavlath, G.K.; English, A.W. Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter. J. Appl. Physiol. 2000, 89, 251–258. [Google Scholar] [CrossRef]
Daniels, D.W.; Tian, Z.; Barton, E.R. Sexual dimorphism of murine masticatory muscle function. Arch. Oral Biol. 2008, 53, 187–192. [Google Scholar] [CrossRef]
Reader, M.; Schwartz, G.; English, A.W. Brief exposure to testosterone is sufficient to induce sex differences in the rabbit masseter muscle. Cells Tissues Organs 2001, 169, 210–217. [Google Scholar] [CrossRef]
Haizlip, K.M.; Harrison, B.C.; Leinwand, L.A. Sex-based differences in skeletal muscle kinetics and fiber-type composition. Physiology 2015, 30, 30–39. [Google Scholar] [CrossRef]
Mariuba, M.V.; Goulart-Silva, F.; Bordin, S.; Nunes, M.T. Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system. Braz. J. Med. Biol. Res. 2011, 44, 694–699. [Google Scholar] [CrossRef]
Cairns, S.P.; Dulhunty, A.F. The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat. Brit. J. Pharmacol. 1993, 110, 1133–1141. [Google Scholar] [CrossRef] [PubMed]
Grassi, C.; Deriu, F.; Artusio, E.; Passatore, M. Modulation of the jaw jerk reflex by the sympathetic nervous system. Arch. Ital. Biol. 1993, 131, 213–226. [Google Scholar] [PubMed]
Ohnuki, Y.; Umeki, D.; Cai, W.; Kawai, N.; Mototani, Y.; Shiozawa, K.; Jin, H.L.; Fujita, T.; Tanaka, E.; Saeki, Y.; Okumura, S. Role of masseter muscle β₂-adrenergic signaling in regulation of muscle activity, myosin heavy chain transition, and hypertrophy. J. Pharmacol. Sci. 2013, 123, 36–46. [Google Scholar] [CrossRef] [PubMed]
Ohnuki, Y.; Umeki, D.; Mototani, Y.; Jin, H.; Cai, W.; Shiozawa, K.; Suita, K.; Saeki, Y.; Fujita, T.; Ishikawa, Y.; Okumura, S. Role of cyclic AMP sensor Epac1 in masseter muscle hypertrophy and myosin heavy chain transition induced by β2-adrenoceptor stimulation. J. Physiol. 2014, 592, 5461–5475. [Google Scholar] [CrossRef]
Umeki, D.; Ohnuki, Y.; Mototani, Y.; Shiozawa, K.; Fujita, T.; Nakamura, Y.; Saeki, Y.; Okumura, S. Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle. J. Pharmacol. Sci. 2013, 122, 278–288. [Google Scholar] [CrossRef]
Noden, D.M.; Marcucio, R.; Borycki, A.G.; Emerson, C.P.J. Differentiation of avian craniofacial muscles: I. Patterns of early regulatory gene expression and myosin heavy chain synthesis. Dev. Dyn. 1999, 216, 96–112. [Google Scholar] [CrossRef]
Lucas, C.A.; Rughani, A.; Hoh, J.F.Y. Expression of extraocular myosin heavy chain in rabbit laryngeal muscle. J. Muscle Res. Cell Motil. 1995, 16, 368–378. [Google Scholar] [CrossRef]
DelGaudio, J.M.; Sciote, J.J.; Carroll, W.R.; Escalmado, R.M. Atypical myosin heavy chain in rat laryngeal muscle. Ann. Otol. Rhinol. Laryngol. 1995, 104, 237–245. [Google Scholar] [CrossRef]
Briggs, M.M.; Schachat, F. Early specialization of the superfast myosin in extraocular and laryngeal muscles. J. Exp. Biol. 2000, Pt 16, 2485–2494. [Google Scholar] [CrossRef]
Hangai, K.; Kobayashi, Y.; Nonaka, S. Developmental changes in histochemical properties of intrinsic laryngeal muscles in rats. Auris Nasus Larynx 1999, 26, 467–478. [Google Scholar] [CrossRef]
Shiotani, A.; Flint, P.W. Expression of extraocular-superfast-myosin heavy chain in rat laryngeal muscles. Neuroreport 1998, 9, 3639–3642. [Google Scholar] [CrossRef]
Jung, H.H.; Lieber, R.L.; Ryan, A.F. Quantification of myosin heavy chain mRNA in somatic and branchial arch muscles using competitive PCR. Am. J. Physiol. 1998, 1 Pt 1, C68–74. [Google Scholar] [CrossRef]
Ferretti, R.; Marques, M.J.; Pertille, A.; Santo Neto, H. Sarcoplasmic-endoplasmic-reticulum Ca²⁺-ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin-deficient mdx mice. Muscle Nerve 2009, 39, 609–615. [Google Scholar] [CrossRef]
Toniolo, L.; Maccatrozzo, L.; Patruno, M.; Caliaro, F.; Mascarello, F.; Reggiani, C. Expression of eight distinct MHC isoforms in bovine striated muscles: evidence for MHC-2B presence only in extraocular muscles. J. Exp. Biol. 2005, Pt 22, 4243–4253. [Google Scholar] [CrossRef]
Brandon, C.A.; Rosen, C.; Georgelis, G.; Horton, M.J.; Mooney, M.P.; Sciote, J.J. Staining of human thyroarytenoid muscle with myosin antibodies reveals some unique extrafusal fibers, but no muscle spindles. J. Voice 2003, 17, 245–254. [Google Scholar] [CrossRef]
Horton, M.J.; Rosen, C.; Close, J.M.; Sciote, J.J. Quantification of myosin heavy chain RNA in human laryngeal muscles: differential expression in the vertical and horizontal posterior cricoarytenoid and thyroarytenoid. Laryngoscope 2008, 118, 472–477. [Google Scholar] [CrossRef] [PubMed]
Han, Y.; Wang, J.; Fischman, D.A.; Biller, H.F.; Sanders, I. Slow tonic muscle fibers in the thyroarytenoid muscles of human vocal folds; a possible specialization for speech. Anat. Rec. 1999, 256, 146–157. [Google Scholar] [CrossRef]
Sokoloff, A.J.; Li, H.; Burkholder, T.J. Limited expression of slow tonic myosin heavy chain in human cranial muscles. Muscle Nerve 2007, 36, 183–189. [Google Scholar] [CrossRef] [PubMed]
Hoh, J.F.Y. Laryngeal muscles as highly specialized organs in airway protection, respiration and phonation. In Handbook of Mammalian Vocalization: An Integrated Neuroscience Approach; Brudzynski, S.M. Ed. Academic Press: London, 2010; pp. 13–22. [Google Scholar]
Ibebunjo, C. Histochemical and morphometric properties of muscles of the upper airway of goats. Res.Vet. Sci. 1993, 55, 215–223. [Google Scholar] [CrossRef]
Li, Z.B.; Lehar, M.; Nakagawa, H.; Hoh, J.F.Y.; Flint, P.W. Differential expression of myosin heavy chain isoforms between abductor and adductor muscles in the human larynx. Otolaryngol--Head Neck Surg. 2004, 130, 217–222. [Google Scholar] [CrossRef] [PubMed]
Wu, Y.Z.; Baker, M.J.; Crumley, R.L.; Caiozzo, V.J. Single-fiber myosin heavy-chain isoform composition of rodent laryngeal muscle: modulation by thyroid hormone. Arch. Otolaryngol. Head Neck Surg. 2000, 126, 874–880. [Google Scholar] [CrossRef] [PubMed]
Rhee, H.S.; Lucas, C.A.; Hoh, J.F.Y. Fiber types in rat laryngeal muscles and their transformations after denervation and reinnervation. J. Histochem. Cytochem. 2004, 52, 581–590. [Google Scholar] [CrossRef] [PubMed]
Wu, Y.Z.; Crumley, R.L.; Caiozzo, V.J. Are hybrid fibers a common motif of canine laryngeal muscles? Single-fiber analyses of myosin heavy-chain isoform composition. Arch. Otolaryngol. Head Neck Surg. 2000, 126, 865–873. [Google Scholar] [CrossRef] [PubMed]
Rhee, H.S.; Steel, C.M.; Derksen, F.J.; Robinson, N.E.; Hoh, J.F.Y. Immunohistochemical analysis of laryngeal muscles in normal horses and horses with subclinical recurrent laryngeal neuropathy. J. Histochem Cytochem. 2009, 57, 787–800. [Google Scholar] [CrossRef]
Sciote, J.J.; Morris, T.J.; Brandon, C.A.; Horton, M.J.; Rosen, C. Unloaded shortening velocity and myosin heavy chain variations in human laryngeal muscle fibers. Ann. Otol. Rhinol. Laryngol. 2002, 111, 120–127. [Google Scholar] [CrossRef] [PubMed]
Wu, Y.Z.; Crumley, R.L.; Armstrong, W.B.; Caiozzo, V.J. New perspectives about human laryngeal muscle: single-fiber analyses and interspecies comparisons. Arch. Otolaryngol. Head Neck Surg. 2000, 126, 857–864. [Google Scholar] [CrossRef] [PubMed]
D'Antona, G.; Megighian, A.; Bortolotto, S.; Pellegrino, M.A.; Ragona, R.M.; Staffieri, A.; Bottinelli, R.; Reggiani, C. Contractile properties and myosin heavy chain isoform composition in single fibre of human laryngeal muscles. J. Muscle Res. Cell Motil. 2002, 23, 187–195. [Google Scholar] [CrossRef]
Toniolo, L.; Macchi, V.; Porzionato, A.; Paoli, A.; Marchese-Ragona, R.; De Caro, R.; Reggiani, C. Myosin heavy chain isoforms in human laryngeal muscles: an expression study based on gel electrophoresis. Int. J. Mol. Med. 2008, 22, 375–379. [Google Scholar] [CrossRef]
Smerdu, V.; Cvetko, E. Myosin heavy chain-2b transcripts and isoform are expressed in human laryngeal muscles. Cells Tissues Organs 2013, 198, 75–86. [Google Scholar] [CrossRef]
Perie, S.; Agbulut, O.; Lacau St Guily, J.; Butler-Browne, G.S. Myosin heavy chain expression in human laryngeal muscle fibers. A biochemical study. Ann. Otol. Rhinol. Laryngol. 2000, 109, 216–220. [Google Scholar] [CrossRef]
Luschei, E.S.; Ramig, L.O.; Baker, K.L.; Smith, M.E. Discharge characteristics of laryngeal single motor units during phonation in young and older adults and in persons with parkinson disease. J. Neurophysiol. 1999, 81, 2131–2139. [Google Scholar] [CrossRef] [PubMed]
Green, J.H.; Neil, E. The respiratory function of the laryngeal muscles. J. Physiol. 1955, 129, 134–141. [Google Scholar] [CrossRef] [PubMed]
Gunn, H.M. Histochemical observations on laryngeal skeletal muscle fibres in 'normal' horses. Equine Vet. J. 1972, 4, 144–148. [Google Scholar] [CrossRef] [PubMed]
Carraro, U.; Catani, C.; Saggin, L.; Zrunek, M.; Szabolcs, M.; Gruber, H.; Streinzer, W.; Mayr, W.; Thoma, H. Isomyosin changes after functional electrostimulation of denervated sheep muscle. Muscle Nerve 1988, 11, 1016–1028. [Google Scholar] [CrossRef] [PubMed]
DelGaudio, J.M.; Sciote, J.J. Changes in myosin expression in denervated laryngeal muscle. Ann. Otol. Rhinol. Laryngol. 1997, 106, 1076–1081. [Google Scholar] [CrossRef] [PubMed]
Wu, Y.Z.; Baker, M.J.; Marie, J.P.; Crumley, R.; Caiozzo, V.J. The plasticity of denervated and reinnervated laryngeal muscle: focus on single-fiber myosin heavy-chain isoform expression. Arch. Otolaryngol. Head Neck Surg. 2004, 130, 1070–1082. [Google Scholar] [CrossRef] [PubMed]
Qiu, X.; Chen, D.; Li, M.; Gao, Y.; Liu, F.; Zheng, H.; Chen, S. Transition of myosin heavy chain isoforms in human laryngeal abductors following denervation. Eur. Arch. Otorhinolaryngol. 2015, 272, 2915–2923. [Google Scholar] [CrossRef]
Davis, P.J.; Macefield, G.; Nail, B.S. Laryngeal motoneurone activity in the rabbit during asphyxic gasping. Respir. Physiol. 1987, 70, 327–342. [Google Scholar] [CrossRef]
Inagi, K.; Connor, N.P.; Schultz, E.; Ford, C.N.; Cook, C.H.; Heisey, D.M. Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx. Otolaryngol--Head Neck Surg. 1999, 120, 876–883. [Google Scholar] [CrossRef] [PubMed]
Paniello, R.C.; West, S.E.; Lee, P. Laryngeal reinnervation with the hypoglossal nerve. I. Physiology, histochemistry, electromyography, and retrograde labeling in a canine model. Ann. Otol. Rhinol. Laryngol. 2001, 110, 532–542. [Google Scholar] [CrossRef] [PubMed]
Dawson, T.J.; Hulbert, A.J. Standard metabolism, body temperature, and surface areas of Australian marsupials. Am. J. Physiol. 1970, 218, 1233–1238. [Google Scholar] [CrossRef]
Kleiber, M. The fire of life. An introduction to animal energetics; Wiley: New York, 1961; p. 454. [Google Scholar]
Schmidt-Nielsen, K. Scaling. Why is Animal Size so Important; Cambridge University Press: Cambridge, 1984. [Google Scholar]
Savage, V.M. Gillooly, J.F. Woodruff, W.H. west, G.B. Allen, A.P. Enquist, B.J. and Brown, J.H. The predominance of quarter-power scaling in biology. Funct. Ecol. 2004, 18, 257–282. [Google Scholar] [CrossRef]
McMahon, T. Size and shape in biology. Science 1973, 179, 1201–1204. [Google Scholar] [CrossRef] [PubMed]
Stahl, W.R. Scaling of respiratory variables in mammals. J. Appl. Physiol. 1967, 22, 453–460. [Google Scholar] [CrossRef]
Pellegrino, M.A.; Canepari, M.; Rossi, R.; D'Antona, G.; Reggiani, C.; Bottinelli, R. Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles. J. Physiol. 2003, Pt 3, 677–689. [Google Scholar] [CrossRef]
Cooper, D.S.; Shindo, M.; Sinha, U.; Hast, M.H.; Rice, D.H. Dynamic properties of the posterior cricoarytenoid muscle. Ann. Otol. Rhinol. Laryngol. 1994, 103, 937–944. [Google Scholar] [CrossRef]
Savolainen, J.; Vornanen, M. Fiber types and myosin heavy chain composition in muscles of common shrew (Sorex araneus). J. Exp. Zool. 1995, 271, 27–35. [Google Scholar] [CrossRef]
Chikuni, K.; Muroya, S.; Nakajima, I. Absence of the functional myosin heavy chain 2b isoform in equine skeletal muscles. Zoolog. Sci. 2004, 21, 589–596. [Google Scholar] [CrossRef]
Ackermann, M.A.; Kontrogianni-Konstantopoulos, A. Myosin binding protein-C slow is a novel substrate for protein kinase A (PKA) and C (PKC) in skeletal muscle. J. Proteome Res. 2011, 10, 4547–4555. [Google Scholar] [CrossRef] [PubMed]

Table 1. Myosin heavy chain expression repertoires of extraocular, masticatory, laryngeal and cricothyroid/limb muscle allotypes across various species. The myosin heavy chain isoforms are listed approximately in the order of decreasing speed. An ‘X’ indicates that the isoform in question is expressed in adult muscles of the allotype in some species. Within an allotype, the isoform(s) expressed can vary between muscles, and between homologous muscles in different species.

Myosin heavy chain isoform	Extraocular allotype	Masticatory allotype	Laryngeal allotype	Cricothyroid/limb allotype
EO	X		X
2B	X	X	X	X
2X	X	X	X	X
2A	X	X	X	X
Masticatory		X
α-cardiac	X	X
β-slow	X	X	X	X
Neonatal	X	X	X
Embryonic	X
Slow B	X
Slow-tonic	X
nmMyH IIB	X

Table 2. Myotube type, fibre types and MyHC composition in rabbit EOM. The fibre types are classified as in [132], the MyHC composition of gSIFs are based on [89], and those of oSIF, oMIF and gMIF are based on [139] and assuming that slow B MyHC [18] and nmMyH IIB MyHC [14] are expressed in rabbit EOM. MyHC components are listed in the order of decreasing speed, minor and variable components are in parentheses).

Myotube type	Fibre type	MyHC composition
Primary	oMIF Central segment End segments	α-cardiac α-cardiac, β-slow, emb, slow B, slow-tonic,
Secondary	oSIF Central segment End segments	EO 2A, emb, slow B, (neo)
Primary	gMIF Central segment End segments	α-cardiac, β-slow, α-cardiac, β-slow, emb, slow-tonic, nmMyH IIB
Secondary	gSIF-red	(2X), 2A, (neo)
Secondary	gSIF-intermediate	(2B), 2X, (2A, neo)
Secondary	gSIF-white	EO, 2B, (2X)

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Developmental, Physiologic and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles

Abstract

1. Craniofacial Muscles and Their Developmental Origins

2. Myosin Heavy Chain and Light Chain Isoforms and Their Genes

3. Kinetic Properties of Myosin Isoforms

4. Modulation of Contractility by Thick Filament Proteins

5. MyHC Expression Repertoire of Craniofacial Muscles

6. Craniofacial Muscle Allotypes

7. Developmental Origin of EOMs

8. Ontogeny of EOMs

9. Neural Regulation of MyHC Expression during EOM Myogenesis: An Hypothesis

10. Functional Demands on EOMs

11. EOM Fibre Types

12. Ocular Motoneurons Innervating MIFs and SIFs

13. Longitudinal Variations in EOM Fibre Characteristics and Their Functional Significance

14. Regulation of MyHC Expression in EOM

15. Developmental Origins of Jaw Muscles

16. Functional Demands on Mammalian Jaw Muscles

17. Fibre Types in Jaw-Closing Muscles of Carnivores

18. Ontogeny of Jaw-Closing Muscles in Carnivores

19. Mechanical Properties of Masticatory Fibres of Carnivores

20. Mechanical Properties of Jaw-Slow Fibres of Carnivores

21. Neural Regulation of Masticatory and Jaw-Slow Fibres of Carnivores

22. Expression of Masticatory Myosin among Vertebrates

23. Phylogenetic Plasticity of Mammalian Jaw-Closing Muscles

24. Development and Regulation of Myosin Expression in Jaw-Closing Muscles in Animals Not Expressing Masticatory Myosin

25. Intrinsic Laryngeal Muscles and Their Functions

26. Developmental Origins of Laryngeal Muscles

27. MyHC Expression Repertoire of Laryngeal Muscles

28. Variations in MyHC Expression in Laryngeal Muscles

29. Functional Significance of Variations in MyHC Expression of Laryngeal Muscles within Species

30. Regulation of MyHC Expression in Laryngeal Muscles within Species

31. Functional Significance of Variations in MyHC Expression in Laryngeal Muscles between Species

32. Regulation of MyHC Expression in Laryngeal Muscles between Species

33. Overview of Myosin Expression Mechanisms in Craniofacial Muscles

34. Future Directions

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