The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segre gate neural crest cells from multipotential dorsal progenitors within the n eural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not exp ressed in regions of Pax3 mutant juice that lack neural crest, implying tha t Foxd3 may regulate aspects of the neural crest differentiation program. W e show that misexpression of Foxd3 in the chick neural tube promotes a neur al crest-like phenotype and suppresses interneuron differentiation. Cells t hat ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emig rate from the neural tube at multiple dorsoventral levels. Foxd3 does not i nduce Slug and RhoB, nor is its ability to promote a neural crest-like phen otype enhanced by co-expression of Slug. Together these results suggest Fox d3 can function independently of Slug and RhoB to promote the development o f neural crest cells from neural tube progenitors.