Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex

Formation of the normal mammalian cerebral cortex requires the migration of GABAergic inhibitory interneurons from an extracortical origin, the latera l ganglionic eminence (LGE). Mechanisms guiding the migratory direction of these neurons, or other neurons in the neocortex, are not well understood. We have used an explant assay to study GABAergic neuronal migration and fou nd that the ventricular zone (VZ) of the LGE is repulsive to GABAergic neur ons. Furthermore, the secreted protein Slit is a chemorepellent guiding the migratory direction of GABAergic neurons, and blockade of endogenous Slit signaling inhibits the repulsive activity in the VZ. These results have rev ealed a cellular source of guidance for GABAergic neurons, demonstrated a m olecular cue important for cortical development, and suggested a guidance m echanism for the migration of extracortical neurons into the neocortex.