Cardiac Neural Crest in Evolution and Development

Cardiac neural crest cells originate from the postotic hindbrain and migrate through the caudal branchial or pharyngeal arches. Some of the cells maintain residence in the arches while others migrate on to the arterial pole of the heart. The cells that remain in the arches participate in development of the arch arteries, thymus and parathyroid glands and have an important role in modulating signaling. Signal modulation in the pharynx is critical for normal proliferation, migration and differentiation of myocardium added to the arterial pole of the heart during looping. In animals with divided systemic and pulmonary blood flow, the cardiac crest cells that continue to migrate from the pharynx into the arterial pole form the aorticopulmonary and conotruncal septa which are responsible for this division. Cardiac neural crest cells that have migrated to the arterial pole are found in the remodeling valve leaflets of all vertebrates that have been studied regardless of whether they form an outflow septum. In addition to providing the cells for septation, cardiac crest cells provide the parasympathetic postganglionic neurons and Schwann cells to the heart. New evidence indicates that neural crest cells may be involved in insulation of the His bundle and conduction tissue. A late wave of migrating cardiac crest cells populates the inflow pole of the heart and these, rather than cells migrating through the arterial pole, may actually contribute to the development of the conduction system. In animals with undivided outflow circulation the roles of cardiac crest cells in heart development is less well understood. However, in zebrafish cardiac crest cells appear to be capable of migrating into the cardiogenic field and differentiating as cardiac myocytes. The genes that control behavior of the cardiac crest in the pharynx and heart include AP2 and Sox transcription factors and retinoic acid signaling for normal development.