Signals controlling neural crest contributions to the heart

Cardiac neural crest cells represent a unique subpopulation of cranial neural crest cells that are specified, delaminate and migrate from the developing neural tube to the caudal pharynx where they support aortic arch artery development. From the caudal pharynx, a subset of these cells migrates into the cardiac outflow tract where they are needed for outflow septation. Many signaling factors are known to be involved in specifying and triggering the migration of neural crest cells. These factors have not been specifically studied in cardiac crest but are assumed to be the same as for the other regions of crest. Signaling factors like Ephs and Semaphorins guide the cells into the caudal pharynx. Support of the cells in the pharynx is from endothelin, PDGF and the TGFbeta/BMP signaling pathways. Mutants in the TGFbeta/BMP pathway show abnormal migration or survival in the pharynx, whereas the migration of the neural crest cells into the outflow tract is orchestrated by Semaphorin/Plexin signaling. Although TGFbeta family members have been well studied and show defective neural crest function in outflow septation, their mechanism of action remains unclear.