Version 1
: Received: 31 July 2024 / Approved: 1 August 2024 / Online: 2 August 2024 (02:38:21 CEST)
How to cite:
Caño-Carrillo, S.; Garcia-Padilla, C.; Aranega, A. E.; Lozano-Velasco, E.; Franco, D. Divergent Transcriptional Regulation and Functional Role of Chick WT1_76127 and Mouse Gm14014 lncRNAs in Epicardial Cell Migration. Preprints2024, 2024080067. https://doi.org/10.20944/preprints202408.0067.v1
Caño-Carrillo, S.; Garcia-Padilla, C.; Aranega, A. E.; Lozano-Velasco, E.; Franco, D. Divergent Transcriptional Regulation and Functional Role of Chick WT1_76127 and Mouse Gm14014 lncRNAs in Epicardial Cell Migration. Preprints 2024, 2024080067. https://doi.org/10.20944/preprints202408.0067.v1
Caño-Carrillo, S.; Garcia-Padilla, C.; Aranega, A. E.; Lozano-Velasco, E.; Franco, D. Divergent Transcriptional Regulation and Functional Role of Chick WT1_76127 and Mouse Gm14014 lncRNAs in Epicardial Cell Migration. Preprints2024, 2024080067. https://doi.org/10.20944/preprints202408.0067.v1
APA Style
Caño-Carrillo, S., Garcia-Padilla, C., Aranega, A. E., Lozano-Velasco, E., & Franco, D. (2024). Divergent Transcriptional Regulation and Functional Role of Chick WT1_76127 and Mouse Gm14014 lncRNAs in Epicardial Cell Migration. Preprints. https://doi.org/10.20944/preprints202408.0067.v1
Chicago/Turabian Style
Caño-Carrillo, S., Estefanía Lozano-Velasco and Diego Franco. 2024 "Divergent Transcriptional Regulation and Functional Role of Chick WT1_76127 and Mouse Gm14014 lncRNAs in Epicardial Cell Migration" Preprints. https://doi.org/10.20944/preprints202408.0067.v1
Abstract
Background: Cardiac development is a complex developmental process. The early cardiac straight tube is composed of an external myocardial layer and an internal endocardial lining. Soon after rightward looping, the embryonic heart becomes externally covered by a new epithelial lining, the embryonic epicardium. A subset of these embryonic epicardial cells migrate and colonize the embryonic myocardium, contributing to distinct cell types. In recent years, our understanding of the molecular mechanisms that govern proepicardium and embryonic epicardium formation has greatly increased. We have recently witnessed a novel layer of complexity governing gene regulation with the discovery of non-coding RNAs. Our laboratory recently identified three distinct lncRNAs, adjacent to the Wt1, Bmp4 and Fgf8 chicken gene loci, with enhanced expression in the proepicardium that are distinctly regulated by Bmp, Fgf and thymosin 4, providing support of their plausible implication in epicardial formation.
Methods: Expression of lncRNAs was analyzed in different chicken and mouse tissues as well as their subcellular distribution in chicken proepicardial, epicardial, ventricle explants and in different murine cardiac cell types. lncRNA transcriptional regulation was analyzed by using siRNAs and expression vectors of different transcription factors in chicken and mouse. Antisense oligonucleotides were used to inhibit Gm14014 expression. Cardiac injury was induced ex vivo in mouse ventricle explants by cryoinjury. Furthermore, RT-qPCR, immunocytochemistry, RNA pulldown, Western blot, viability and cell migration assays were conducted to investigate the biological function of Wt1_76127 and Gm14014.
Results: We demonstrated that Wt1_76127 in chicken and its evolutionarily conserved homologue Gm14014 in mice are widely distributed in different embryonic and adult tissues and distinctly regulated by cardiac enriched transcription factors, particularly Mef2c and Nkx2.5. Gm14014 is distinctly regulated in mouse ventricular cryoinjury ex vivo models, displaying a negative correlation with epicardial and epithelial to mesenchymal transition markers. Furthermore, silencing assays demonstrated that mouse Gm14014, but not chicken Wt1_76127, is essential for epicardial, but not endocardial or myocardial cell migration. Such process is governed by partnering with Myl9, promoting cytoskeletal remodeling.
Conclusion: Our data evidence that Gm14014 plays a pivotal role in epicardial cell migration essential for heart regeneration.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
