Birth defects are the most common cause of infant death in the United States, affecting 120,000 children each year. Many birth defects occur because "neural crest" cells do not divide, migrate or differentiate normally during development. Neural crest cells form many critical structures, including the great vessels of the heart and the enteric nervous system (ENS), which controls the digestive system. We are focused on understanding the genes that control the normal development of these two key tissues. Recent technical advances in stem cell biology give hope that we can regenerate tissues that did not form properly. However, we do not yet know how to convert undifferentiated neural crest cells into the specific cell types that are needed, nor do we understand the genetic mechanisms of their disruption in patients.
- We developed tools and defined in vivo gene expression profiles of crest derived cells
- Key genes expressed in these cells were tested to determine if they are necessary and sufficient for specifying cell fate
- Key genes were tested using human genetics for contribution to ENS and cardiac phenotypes
Potential impact: Abnormal development of crest derived tissues can lead to life threatening problems, including Hirschsprung disease and supravalvar aortic stenosis. Our work will help define genetic causes of disease in patients and identify mechanisms for differentiating replacement cells.