A novel role for cardiac neural crest in heart development

Ablation of premigratory cardiac neural crest results in defective developm ent: of the cardiac outflow tract, The purpose of the present study was to correlate the earliest functional and morphological changes in heart develo pment after cardiac neural crest ablation. Within 24 hours after neural cre st ablation, the external morphology of the hearts showed straight outflow limbs, tighter heart loops, and variable dilations. Incorporation of bromod eoxyuridine in myocytes, an indication of proliferation, was doubled after cardiac neural crest ablation. The myocardial calcium transients, which are a measure of excitation-contraction coupling, were depressed by 50% in bot h the inflow and outflow portions of the looped heart tube. The myocardial transients could be rescued by replacing the cardiac neural crest. The card iac jelly produced by the myocardium was distributed in an uneven, rather t han uniform, pattern. An extreme variability in external morphology could b e attributed to the uneven distribution of cardiac jelly. In the absence of cardiac neural crest, the myocardium was characterized by somewhat disorga nized myofibrils that may be a result of abnormally elevated proliferation. In contrast, endocardial development appeared normal, as evidenced by norm al expression of fibrillin-2 protein (JB3 antigen) and normal formation of cushion mesenchyme and trabeculae. The signs of abnormal myocardial develop ment coincident with normal endocardium suggest that the presence of cardia c neural crest cells is necessary for normal differentiation and function o f the myocardium during early heart development. These results indicate a n ovel role for neural crest cells in myocardial maturation.