Figure 1.

Neural crest formation and migration during development. Neural crest regionalization (top) at the boundary of the neural plate and epidermis is a multi-step process. First, the border of the neural plate is set via secretion of neural plate inductive signals (Fgf, Bmp, and Wnt) from the ventral ectoderm and paraxial mesoderm (not shown). Anteriorly, the timing of Bmp and Wnt signaling contributes toward setting the boundaries between epidermis, prospective neural crest, and neural plate. In the narrow band, where Wnt signaling induces Bmp signaling and Wnt signaling is not subsequently turned off, NCCs are formed. Bmp, Wnt, and Fgf, which are secreted by the prospective neural crest, induce the expression of border regionalization genes such as Msx1/2, Pax3/7, and Zic1. In contrast, in the epidermis high concentrations of Bmp induce the expression Msx1/2, which promote keratin expression and Dlx3/5, which induce Zic1 and Sox2 expression. Neural crest specification (middle) starts with the expression of FoxD3, Slug/Snail, c-Myc, Sox9, and Id by the border cells, which prevents this region from becoming either neural plate or epidermal tissue. EMT, delamination, and migration of NCCs (bottom), is primarily induced by FoxD3, Snail, and Sox9. These factors are also capable of inducing a cranial neural crest fate for cells of the lateral neural tube, when ectopically expressed in this region. After delamination NCCs migrate to their respective destinations, regulated by the expression of proteins such as FoxD3, SoxE, Cad6/7, Nrp, and Eph receptors. Specifically, the head and facial structures are largely products of the cranial neural crest, which is a mixed population of cells, with about 10% of these cells being multipotent progenitor cells.