Scratch regulates neuronal migration onset via an epithelial-mesenchymal transition-like mechanism.

During neocortical development, the neuroepithelial or neural precursor cells that commit to neuronal fate need to delaminate and start migration toward the pial surface. However, the mechanism that couples neuronal fate commitment to detachment from the neuroepithelium remains largely unknown. Here we show that Scratch1 and Scratch2, members of the Snail superfamily of transcription factors, are expressed upon neuronal fate commitment under the control of proneural genes and promote apical process detachment and radial migration in the developing mouse neocortex. Scratch-induced delamination from the apical surface was mediated by transcriptional repression of the adhesion molecule E-cadherin. These findings suggest that Scratch proteins constitute a molecular link between neuronal fate commitment and the onset of neuronal migration. On the basis of their similarity to proteins involved in the epithelial-mesenchymal transition (EMT), we propose that Scratch proteins mediate the conversion of neuroepithelial cells to migrating neurons or intermediate neuronal progenitors through an EMT-related mechanism.