Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs) such boundaries produce mosaic patterns of investment based on embryonic origins with important implications for the non-uniform distribution of vascular disease later in life. Morphogenesis of blood vessels requires vascular cell movements within compartments as highly-sensitive responses to changes in fluid flow shear stress and wall strain. These movements underlie remodeling of primitive plexuses, expansion of lumen diameters, regression of unused vessels, and building multilayered artery walls. Although loss of endothelial compartment boundaries can produce arterial-venous malformations, little is known about the consequences of mislocalization or failure to form SMC origin-specific boundaries during vascular development. We propose that the failure to establish a normal compartment boundary between cardiac neural crest-derived SMCs of the 6th pharyngeal arch artery (future ductus arteriosus) and paraxial mesoderm-derived SMCs of the dorsal aorta in mid-gestation embryos leads to aortic coarctation observed at birth. This model raises new questions about the effects of fluid flow dynamics on SMC investment and the formation of SMC compartment borders during pharyngeal arch artery remodeling and vascular development.