Modes of neuronal migration in the developing cerebral cortex

Key Points In the developing nervous system, two modes of migration have been identified: radial and tangential. Radial migration is the principal mode of migration in the developing cerebral cortex, although the GABA (γ-aminobutyric acid)-expressing interneurons, which arise in the ventral telencephalon, migrate tangentially into the cortex. Layers II–VI of the mammalian cortex are generated in an 'inside-out' sequence, such that early-born cells reside in the deepest layers, whereas later-born cells migrate past the existing layers to form the superficial layers. Radially migrating neurons adopt two separate modes of movement: somal translocation during the early stages of corticogenesis; and glia-guided migration during the later stages, when the cerebral wall is considerably thicker. Evidence for somal translocation came from the reeler mouse and from other mutants that have abnormal cortical lamination. Although these mutations disrupt glia-guided migration, the preplate forms normally, indicating that another mode of radial migration is required for the early stages of cortical lamination. Translocation might be an older mode of movement in the evolution of the cerebral cortex for the transfer of preplate and early cortical-plate neurons, whereas glia-guided migration might have evolved to guide cells across more complex paths during late corticogenesis. Little is known about how tangentially migrating interneurons integrate into specific cortical layers. A recent study has shown that they migrate towards the cortical ventricular zone, a mode of movement termed 'ventricle-directed migration'. Here, they might receive layer information that is essential for their correct integration. The next challenge will be to establish where they acquire spatial information, and what signals guide them to their correct positions. The conventional scheme of cortical formation shows that postmitotic neurons migrate away from the germinal ventricular zone to their positions in the developing cortex, guided by the processes of radial glial cells. However, recent studies indicate that different neuronal types adopt distinct modes of migration in the developing cortex. Here, we review evidence for two modes of radial movement: somal translocation, which is adopted by the early-generated neurons; and glia-guided locomotion, which is used predominantly by pyramidal cells. Cortical interneurons, which originate in the ventral telencephalon, use a third mode of migration. T