The neural crest is a population of cells that migrates from the dorsal neural tube and gives rise to cells of the peripheral nervous system, as well as to a variety of non-neural lineages. Because it contributes to so many different tissues, its correct specification and deployment are of vital importance to the developing embryo. The factors that specify neural crest are largely unknown, but several candidates are beginning to emerge. One of the strongest candidates is the winged-helix transcription factor Foxd3, and a study by Dottori et al. has shed new light on its role in neural crest specification in chick and mouse embryos.

Dottori et al. showed that Foxd3 expression marks both premigratory and migrating neural crest cells in the mouse embryo. These Foxd3-expressing cells can give rise to a variety of cell lineages, including sensory/sympathetic neurons, glia and melanocytes.

By electroporating a Foxd3 expression construct into chick embryos, the authors showed that Foxd3 could induce ectopic expression of neural-crest-specific markers, such as HNK1 and CAD7, along the entire dorsoventral axis of the neural tube. Moreover, the electroporated cells were able to delaminate and migrate away from the neuroepithelium. Also, there was a considerable reduction in the number of cells expressing interneuron-specific markers in the electroporated side of the neural tube, indicating that Foxd3 also suppresses interneuron differentiation.

The Pax3 transcription factor is thought to specify dorsal cell fate in the neural tube. Dettori et al. showed that in Pax3 knockout mice, Foxd3 expression was absent caudal to the hindbrain/spinal cord boundary, and that this region also failed to generate neural crest. This provides additional support for a role of Foxd3 in neural crest specification, and places it downstream of Pax3.

Dorsal neuroepithelial cells have several fate choices; they could become neural crest, interneurons or roof-plate cells. Dottori et al. have shown that Foxd3 seems to have a dual role in dorsal cell specification — promoting neural crest cell fate and inhibiting interneuron differentiation. Foxd3 is clearly sufficient to transform neuroepithelial cells into neural crest, but is it necessary? Expression of a Foxd3 repressor in Xenopus has already been shown to inhibit neural crest formation, and it will be interesting to see whether inactivating Foxd3 has a similar effect in the mouse or the chick.