• Notch signaling;
  • neural crest;
  • cardiovascular malformation;
  • migration;
  • differentiation;
  • neurocristopathy


Background: The function of Notch signaling in murine neural crest–derived cell lineages in vivo was examined. Results: Conditional gain (Wnt1Cre;RosaNotch) or loss (Wnt1Cre;RBP-Jf/f) of Notch signaling in neural crest cells (NCCs) in vivo results in craniofacial, cardiac, and trunk abnormalities. Severe craniofacial malformations are apparent in Wnt1Cre;RosaNotch embryos, while less severe skull abnormalities are evident in Wnt1Cre;RBP-Jf/f mice. Deficient cardiac neural crest migration, resulting in cardiac outflow tract malformations, occurs with increased or decreased Notch signaling in NCCs. Smooth muscle cell differentiation also is impaired in pharyngeal NCC derivatives in both Wnt1Cre;RosaNotch and Wnt1Cre;RBP-Jf/f embryos. Neurogenesis is absent and gliogenesis is increased in the dorsal root ganglia of Wnt1Cre;RosaNotch embryos, while neurogenesis is increased and gliogenesis is decreased in Wnt1Cre;RBP-Jf/f embryos. Conclusions: Together, these studies demonstrate essential cell-autonomous roles for appropriate levels of Notch signaling during NCC migration, proliferation, and differentiation with critical implications in craniofacial, cardiac, and neurogenic development and disease. Developmental Dynamics 241:376–389, 2012. © 2011 Wiley Periodicals, Inc.