Neural crest (NC) cells are progenitors that delaminate away from the neural tube once specified. An epithelial to mesenchymal transition is required in these cells before dispersal can occur. These cells then migrate to new locations where they form the peripheral neurons and glia, in addition to several other cell types. On , Kalcheim and colleagues show how BMP4 promotes the ADAM10-mediated cleavage of N-cadherin along the neural tube, thus alleviating the inhibitory effect of N-cadherin on NC delamination. Full-length N-cadherin protein inhibits NC delamination by promoting cell-adhesion mechanisms and by repressing Wnt signalling, which acts downstream of BMP4 and is required for delamination. Mutation analysis revealed that N-cadherin has three domains - the β-catenin, extracellular and juxtamembrane domains that are required for correct NC delamination. Interestingly, overexpression of the N-cadherin soluble cytoplasmic cleavage product stimulates both β-catenin and cyclin D1 transcription, leading to enhanced Wnt signalling and NC delamination.
