Abstract

We are using a multiorganismal approach to examine the role of the cardiac neural crest in heart development and regeneration. Cardiac neural crest cells contribute to important portions of the cardiovascular system including the aorticopulmonary septum and cardiac ganglion. It has previously been shown that surgical ablation of the chick cardiac crest results in failure of this septation process, phenocopying the human heart defect persistent truncus arteriosus, and that trunk neural crest fails to rescue this phenotype. By transcriptionally profiling the cardiac versus trunk neural crest to characterize genes unique to this population, we identify a cardiac crest subcircuit comprised of Tgif1, Sox8, and Ets1 that is sufficient to reprogram the trunk neural crest with the ability to rescue cardiac neural crest ablation. We then use replication incompetent avian retroviruses for precise high-resolution lineage analysis of the cardiac crest in chick and uncover a previously undescribed neural crest contribution to cardiomyocytes of the ventricles, supported by Wnt1-Cre lineage analysis in mice. This raised the intriguing possibility that cardiac neural crest cells may contribute to heart repair. We test this in zebrafish due to their remarkable capacity to regenerate the heart after injury. Whereas the adult heart has few sox10+ neural crest cells, we find that sox10 and other migratory neural crest markers are redeployed shortly after resection in the regenerated trabecular myocardium and ablation of the sox10 positive cells impairs closure of the wound. The results suggest that cardiac neural crest cells contribute to many cardiovascular structures including cardiomyocytes across vertebrates and to the regenerating heart of teleost fish.