Optimization of interneuron function by direct coupling of cell migration and axonal targeting

Neural circuit assembly relies on the precise synchronization of developmental processes such as cell migration and axon targeting, but the cell autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive class of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Alteration of the normal migratory route of Martinotti cells by conditional deletion of Mafb – a gene that is preferentially expressed by these cells – cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.