Neural crest specification: migrating into genomics

Neural crest cells migrate from the neural tube to colonize the far reaches of the embryo, where they form peripheral neurons, glia, connective tissue, bone, secretory cells and the outflow tract of the heart. This article provides an overview of early neural crest development, and discusses how genomic techniques are helping us to understand this process at the genetic level.During neurulation, the neural plate border bends to form the neural folds, which become the dorsal aspect of the neural tube. Depending on the organism and the axial level, neural crest cells initiate migration from the closing neural folds or the dorsal neural tube. Although the neural folds are viewed as 'premigratory' neural crest, only a fraction of these cells will actually migrate.Wnt proteins, bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) mimic the tissue interactions that induce neural crest. The main neural crest-inducing signal from the non-neural ectoderm seems to be a Wnt protein, although the Wnts, BMPs and FGFs might have different roles in neural crest induction and maintenance in different species.Less is known about the events downstream of the signals that induce neural crest, although a growing list of genes has been found to be necessary and/or sufficient to initiate neural crest development. This list includes epidermal, neural and neural crest markers. The relationships between these genes are not clear.Many neural crest genes stimulate proliferation and prevent differentiation (Zic genes, Pax3, c-Myc, Ap2, Msx1 and Msx2, Id2, Notch1 and Twist) or maintain stem cell potential (Foxd3 and Sox10). They include genes for transcriptional repressors (Slug/Snail, Zic1, Msx1 and Msx2, Nbx and Id2) and activators (Sox9 and Sox10, Pax3, c-Myc, Ap2 and Notch1).Genomic level screens could potentially identify all the genes that are involved in early neural crest development, which could then be assembled into functional networks. In chick and Xenopus, it is possible to combine powerful array technologies with experimental embryology, and equally enticing is the intersection of genetics, transgenics and genomics in zebrafish.