The cortical GABAergic interneurons of mouse embryos migrate long distances from the medial ganglionic eminence (MGE) in which they are generated, to the cortex in which they settle. We have recently identified two mechanisms involved in their migration to the cortex.
First we showed that the mother centriole of migrating cortical interneurons assembles and exposes to the cell surface a short primary cilium. Primary cilia are required for Sonic hedgehog (Shh) signal transduction in vertebrates. Shh favored the exit of MGE cells away from their tangential migratory paths in the developing cortex. In contrast, both cyclopamine and the ablation of IFT genes maintained MGE cells in the tangential paths. Our findings show that signals transmitted through the primary cilium promote the escape of future GABAergic interneurons from their tangential routes to colonize the cortical plate.
MGE cells express the cell adhesion molecule N-cadherin. Using N-cadherin-coated substrate, we show that N-cadherin-dependent adhesion promotes the migration of mouse MGE cells in vitro. In vivo, MGE cells with a genetic ablation of N-cadherin showed impaired motility and directionality. Their tangential migration to the cortex was delayed and their capability to invade the developing cortical plate, altered.
Altogether, these results identify N-cadherin and the primary cilium as important regulators of the migration of cortical interneurons in the developing cortex. If both interact functionally remains to be determined.