Birth defects are the most common cause of death in newborns, and many birth defects are caused by problems in neural crest development. The neural crest is a population of cells during fetal development that gives rise to many structures, including the great vessels of the heart, bones of the face, and the nervous system in the bowel (the enteric nervous system or ENS). Since the ENS controls most aspects of intestinal function, ENS defects cause vomiting, constipation, abdominal pain and growth failure. The most severe ENS defects, including Hirschsprung disease, a problem where the ENS is missing from the end of the bowel, can be fatal. New data suggest that defects in metabolism of purines (a component of DNA and RNA) could cause abnormal neural crest development. These data also suggest that deficiency in the vitamin folate might be a risk factor for birth defects affecting the ENS and other neural crest derivatives. Our studies will investigate the role of purine metabolism and folate in ENS development, with the goal of reducing the frequency of severe neural crest associated birth defects.