A role for mDia ,

In brain development, excitatory and inhibitory neurons show distinct types of migration, radial migration and tangential migration, respectively. Whether these two types of migration are operated by similar cellular mechanisms remains unclear. Here we examined mice deficient in mDia, a Rho-regulated actin nucleator, in neuronal migration. mDia deficiency impaired tangential migration of cortical and olfactory inhibitory interneurons, whereas radial migration and consequent layer formation of cortical excitatory neurons were unaffected. mDia-deficient neuroblasts exhibited reduced separation of the centrosome from the nucleus and retarded nuclear translocation. Concomitantly, anterograde F-actin movement and the following rear F-actin condensation that occur during centrosomal and nuclear movement of wild-type cells, respectively, were impaired in mDia-deficient neuroblasts. Blockade of ROCK, another Rho effector regulating myosin II, also impaired nuclear translocation. These results suggest that the Rho-mDia/ROCK signaling critically regulates nuclear translocation via F-actin dynamics in tangential migration, while this mechanism is dispensable in radial migration.