Migration of cortical interneurons relies on branched leading process dynamics

Migrating cells typically reach their targets in response to a relatively wide variety of extracellular molecules. Somehow surprisingly, most cells transduce these extracellular signals into a relatively homogeneous set of cellular changes that allow them to accurately find their target position. Here we summarize the characterization of the migratory behaviour of cortical interneurons in their journey to the cerebral cortex, which seems to represent a novel type of cellular adaptation during directional guidance. Similar to other migrating cells, cortical interneurons are highly polarized cells, with a prominent leading process and a short trailing process. However, the leading process of migrating interneurons continuously branches during the migratory cycle of these cells. Leading process branches are generated in response to the extracellular environment, and seem to serve as the main mechanism that determines the migratory direction for the cell. For each migratory cycle, the branch that is best oriented towards an attractive guidance cue will become stabilized, which in turn will allow the subcellular organelles and the nucleus to progress in the right direction. This migratory process is under the strict control, among several other molecules, of members from the small Rho GTPases family proteins. Pharmacological blocking of ROCKI/II abrogates the formation of leading process branches in migrating interneurons. The resulting cells, with a single leading process, do not efficiently modify their orientation in response to extracellular guidance cues, and so they fail to complete their migration.