Mechanisms of tangential migration of interneurons in the developing forebrain

The formation of functional neuronal networks requires the coordinated migration of neural cells from their birthplaces to final destinations where they differentiate to acquire specific functions. The migration strategy adopted by these different cell types is critical to form and organize tissue domains, preserve topographic information, and favor specific connectivity patterns. The first observations that some neuronal cells also move in nonradial planes in the developing cortical wall, independently of radial glial processes, were made in the 1990s. These neurons were identified as interneurons originating from the ventral forebrain a few years later. Since this discovery, the cellular and molecular characterization of interneuron migration underwent a remarkable development. Tangential migration brings ventrally generated neurons to diverse structures such as the cerebral cortex, striatum, or the olfactory bulb. Some of these regions are located at significant distances from the subpallium; thus, tangential migration is the migration mode of cells that cross boundaries and integrate remarkable molecularly distinct locations. Their ability to cross boundaries overcame the challenge of bringing together cell populations initially segregated in distinct microenvironments contributing for their fate acquisition. Most of the current knowledge regarding routes, guidance, and cellular dynamics of interneuron migration comes from studies conducted in transgenic mice. Here, we present a summary of these studies and a perspective on how new technological developments can soon aid extending the knowledge we have been acquiring to physiological and pathological human models.