The diverse roles of neural crest in cardiovascular development: myocardial function, aortic arch repatterning and outflow septation

Abstract

Ablation of the cardiac neural crest in chick embryos results in abnormal remodeling of the aortic arch arteries and absence of the cardiac outflow septum. These traditional roles of neural crest were described more than a decade ago and with the advent of molecular and transgenic techniques, we are now beginning to unravel the molecular underpinnings of these processes. Recently, it has been shown that cardiac neural crest ablation also results in defects in myocardial development that can be observed as early as stage 14, a stage at which the cardiac neural crest has not yet entered the cardiac outflow tract. These defects, which include reduced contractility, deficient excitation–contraction coupling, as determined by lowered calcium transients, and disorganized contractile apparatus, are likely due to an absence of neural crest-derived cells in the pharyngeal arch region at this stage. In normal embryos, the cardiac neural crest provides a substantial cellular partition interposed between the pharyngeal endoderm, the endothelium of the aortic arch arteries and the aortic sac and the myocardium of the outflow tract. In cardiac neural crest-ablated embryos, the geometry of these elements is disturbed such that the endoderm and endothelium are apposed leaving the myocardial cuff in much closer proximity to the pharyngeal endoderm than normal. New experimental evidence suggests that neural crest cells which normally interpose between the pharyngeal endoderm and the myocardium, suppress a signal, perhaps a growth factor, produced by the pharyngeal endoderm that deleteriously affects further myocardial development.