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

Ablation of the cardiac neural crest in chick embryos results in abnormal r emodeling of the aortic arch arteries and absence of the cardiac outflow se ptum. These traditional roles of neural crest were described more than a de cade ago and with the advent of molecular and transgenic techniques, we are now beginning to unravel the molecular underpinnings of these processes. R ecently, 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 card iac outflow tract. These defects, which include reduced contractility, defi cient excitation-contraction coupling, as determined by lowered calcium tra nsients, and disorganized contractile apparatus, are likely due to an absen ce of neural crest-derived cells in the pharyngeal arch region at this stag e. In normal embryos, the cardiac neural crest provides a substantial cellu lar partition interposed between the pharyngeal endoderm, the endothelium o f the aortic arch arteries and the aortic sac and the myocardium of the out flow tract. In cardiac neural crest-ablated embryos, the geometry of these elements is disturbed such that the endoderm and endothelium are apposed le aving the myocardial cuff in much closer proximity to the pharyngeal endode rm 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 en doderm that deleteriously affects further myocardial development. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.