PAK3 controls the tangential to radial migration switch of cortical interneurons by coordinating changes in cell shape and polarity

Abstract

During the embryonic development, cortical interneurons migrate a long distance tangentially and then re-orient radially to settle in the cortical plate where they contribute to cortical circuits. Migrating interneurons express PAK3, a p21-activated kinase that switches between active and inactive states and controls interneuron migration by unknown mechanism(s). Here we examined the role of the kinase activity of PAK3 to regulate the migration of cortical interneurons. We showed that interneurons expressing a constitutively active PAK3 mutant (PAK3-ca) oriented preferentially radially in the cortex, extended short leading processes and exhibited unstable polarity. On the contrary, interneurons expressing an inactive PAK3 mutant (PAK3-kd for kinase dead) extended branched leading processes, showed directed nuclear movements and remained in the tangential pathways. Results showed that PAK3 kinase activity controls the switch between the tangential and radial modes of migration of cortical interneurons and identified myosin 2B as an effector of this switch.