Regulatory events in neural crest formation and migration

Neural crest cells arise within the ectoderm during neurulation and give rise to most of the peripheral nervous system. Following neural tube closure, they come to lie within the dorsal neural tube from which they emerge and subsequently migrate extensively to numerous and characteristic sites. There, they differentiate into neurons and glia of the peripheral nervous system, cartilage and bone of the face, melanocytes and various other cell types. Inductive interactions between the neural and non‐neural ectoderm can generate neural crest cells, suggesting that signals travel through the epidermis to generate neural crest cells prior to neural tube closure. Induction of the neural crest appears to be a multiphasic process and involves a combination of an early Wnt signal, likely mediated by Wnt6, together with later functions for BMP signaling pathways. We have shown that Wnt is both necessary and sufficient for this induction of the neural crest cells from neural plate tissue. Initiation of neural crest induction appears to begin in the gastrulating embryo and require the transcription factor, Pax7. Finally, we have been taking a genomics approach together with gain‐ and loss‐of‐function experiments to identify the array of molecules expressed as a result of neural crest induction and their subsequent role in neural crest migration. I will discuss how one of the downstream target genes identified in this screen, the neuropilin‐2 receptor, plays a critical role in guidance of neural crest migration. The results suggest that a series of gene regulatory circuits are involved in the production of migratory neural crest cells in the early vertebrate embryo.