Development of the mammalian neocortex involves the radial migration of neurons, which move from their place of birth to their final position in the appropriate neocortical cell layer. This migration is known to involve cadherins but the specific cadherins implicated and the mechanisms by which they act are unclear. Now, on p. , Ulrich Mueller and colleagues report that cadherin 2 (CDH2) and cadherin 4 (CDH4) play crucial roles during radial neuronal migration in the mouse neocortex. The researchers first demonstrate that both CDH2 and CDH4 are expressed in the developing mouse neocortex. The inactivation of Cdh2 or Cdh4 specifically in migrating neurons reveals that both are required for radial migration. The authors further report that CDH2 and CDH4 act via protein tyrosine phosphatase 1B (PTP1B) and α- and β-catenins to control migration. Finally, they show that the perturbation of cadherin-mediated signalling has no effect on the formation or extension of neuronal leading processes but instead disrupts nucleokinesis – the process by which the nucleus translocates forward during migration. These and other findings suggest that cadherin-mediated signalling to the cytoskeleton is crucial for radial migration in the neocortex.
