Conotruncal abnormalities represent profound disturbances of the basic architecture of the heart which occur in a significant numbeer of babies with congenital heart defects. Conotruncal abnormalities include persistent truncus arteriosus, transposition of the great vessels, tetralogy of Fallot and several other congenital heart malformations. The pathogenesis of conotruncal abnormalities is unknown. It has recently been discovered that occipital neural crest cells migrate into the conotruncus and that removal of these cells prior to their migration results in conotruncal malformation. This proposal will further define the extent of this migration and the role of neural crest cells in conotruncal development. Quail neural crest will be transplanted onto chick embryos at varying occipital levels. The quail cells will be mapped in the conotruncus to determine which levels of neural crest contribute to which areas of the conotruncal septum. Parts of occipital neural crest will be removed to determine whether specific lesions are associated with particular areas of neural crest. Various conotruncal teratogens will be studied with regard to their ability to disrupt occipital neural crest migration into the conotruncal region. This proposal represents a two-pronged advance in the area of conotruncal abnormalities in that it will result in a reliable model in which to study the morphogenesis of these abnormalities and it will advance our theories of the pathogenesis of this life-threatening congenital defect.
