A mechanism for inside-out lamination in the neocortex

We outline a unified model for inside-out layering of the neocortex, hinging on a new interpretation for the effects of Reelin on neuronal migrations. The effects of Reelin on cortical structure have been analyzed in great detail, but it has been unclear how individual migrating cells respond to Reelin. In our opinion, many published results might be explained if Reelin acts on neurons when their leading processes reach the marginal zone. Reelin then stimulates two parallel events: detachment from radial glia and translocation of the cell soma to the top of the developing cortical plate. This ‘detach and go’ model explains many aspects of inside-out lamination, defects in the Reeler mutant and results of recent genetic and in utero experiments.