TY - JOUR T1 - JNK signaling regulates cellular mechanics of cortical interneuron migration JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0132-20.2020 SP - ENEURO.0132-20.2020 AU - Skye E. Smith AU - Nicholas K. Coker AU - Eric S. Tucker Y1 - 2020/07/31 UR - http://www.eneuro.org/content/early/2020/07/31/ENEURO.0132-20.2020.abstract N2 - Aberrant migration of inhibitory interneurons can alter the formation of cortical circuitry and lead to severe neurological disorders including epilepsy, autism, and schizophrenia. However, mechanisms involved in directing the migration of interneurons remain incompletely understood. Using a mouse model, we performed live-cell confocal microscopy to explore the mechanisms by which the c-Jun NH2-terminal kinase (JNK) pathway coordinates leading process branching and nucleokinesis, two cell biological processes that are essential for the guided migration of cortical interneurons. Pharmacological inhibition of JNK signaling disrupts the kinetics of leading process branching, rate and amplitude of nucleokinesis, and leads to the rearward mislocalization of the centrosome and primary cilium to the trailing process. Genetic loss of Jnk from interneurons also impairs leading process branching and nucleokinesis, suggesting that important mechanics of interneuron migration depend on the intrinsic activity of JNK. These findings highlight key roles for JNK signaling in leading process branching, nucleokinesis, and the trafficking of centrosomes and cilia during interneuron migration, and further implicates JNK signaling as an important mediator of cortical development.SIGIFICANCE STATEMENT Unlike their excitatory counterparts, inhibitory interneurons are generated in the ventral forebrain and migrate long distances to reach the cerebral cortex. Although many factors influencing the guided migration of cortical interneurons have been elucidated, the role of intracellular signaling pathways in interneuron migration have remained elusive. Here, we show with single cell resolution that the c-Jun NH2-terminal kinase (JNK) signaling pathway coordinates multiple cellular mechanisms that direct the migration of cortical interneurons, including leading process branching, nucleokinesis, and the subcellular positioning of the centrosome-cilia complex. Furthermore, we show that cortical interneuron migration depends on the intrinsic activity of JNK. These results provide new insight into the cellular and molecular mechanisms controlling cortical interneuron migration in normal and pathologic brain development. ER -