Cortical interneurons require JNK signaling for migration regardless of substrate and topographical environment

During embryonic development, cortical interneurons travel tangentially in migratory streams to reach the cerebral cortex, then turn radially to exit their streams and invade the cortical plate. Migrating cortical interneurons remain in constant communication with both extracellular signals and intracellular machinery to maintain a directed migration into the cortical rudiment. In order to engage in directed migration, cortical interneurons undergo the cell biological process termed nucleokinesis in which interneurons translocate their cell bodies into a cytoplasmic swelling formed in the leading process. Many of the intracellular mechanisms governing the timing of migratory stream exit and cortical plate invasion are poorly understood yet are of fundamental importance to cortical development. We previously uncovered a requirement for the c-Jun NH ₂ -terminal kinase (JNK) signaling pathway in cortical interneuron migration. Disruption of the JNK signaling pathway resulted in a delayed entry of cortical interneurons into the cortex, as well as a premature departure from migratory streams. We are interested in uncovering the mechanisms by which JNK activity coordinates the intracellular processes essential for the guided migration of cortical interneurons. Our data shows, through the use of multiple ex vivo and in vitro assays, that cortical interneurons treated with JNK inhibitor exhibit major deficiencies in nucleokinesis. Additionally, we developed a novel tool to explore cortical interneuron migration using a nanopattern topography. Interneurons grown on nanopatterns have significantly faster migratory speeds and translocate further distances than cells cultured on a flat substrate. Interneurons grown on nanopatterns also display a different subcellular distribution of doublecortin, a known target of JNK signaling involved in microtubule stability and the guided migration of cortical interneurons. Overall, our results highlight the importance of JNK signaling in the guided migration of cortical interneurons.