Sonic hedgehog restricts adhesion and migration of neural crest cells independently of the Patched-Smoothened-Gli signaling pathway

In the vertebrate embryo, neural cell types are organized spatially along t he dorsoventral axis of the neural tube and differ by expression of cell-in trinsic determinants and by their adhesive and locomotory properties. Thus, dorsally, neural crest cells (NCC) show a strong propensity to disperse an d migrate, whereas cells situated ventrally are highly cohesive and poorly motile. Members of the bone morphogenetic proteins have been shown to exert a dual role in the specification of dorsal neuroepithelial cells and in th e dispersion of NCCs. To test whether Sonic hedgehog (Shh), another signali ng molecule involved in the patterning of the ventral neural tube, might al so contribute to the control of the adhesive and migratory potential of neu roepithelial cells, we analyzed the effect of ectopic Shh on NCC dispersion from neural tube explants cultured in vitro. The addition of Shh to the mi gration substrate of NCC caused inhibition of their dispersion. The effect of Shh on cell migration was reversible and was not accounted for by altera tions of the specification, delamination, proliferation, and survival of NC Cs but could be essentially attributed to a decreased cell-substrate adhesi on mediated by integrins. In addition, Shh activity on cell migration was m ediated by a specific N-terminal region of the molecule and was independent from the signaling cascade elicited by the Patched-Smoothened receptor and involving the Gli transcription factors. Our study therefore reveals an un anticipated role for Shh in regulating adhesion and migration of neuroepith elial cells that is discernable from its inductive, mitogenic, and trophic functions.