JNK Signaling Regulates Cellular Mechanics of Cortical Interneuron Migration

eNeuro. 2020 Aug 20;7(4):ENEURO.0132-20.2020. doi: 10.1523/ENEURO.0132-20.2020. Print 2020 Jul/Aug.

JNK Signaling Regulates Cellular Mechanics of Cortical Interneuron Migration

Skye E Smith 1 2 3 , Nicholas K Coker 1 , Eric S Tucker 4 3

1Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506.
2Biochemistry and Molecular Biology Graduate Program, West Virginia University School of Medicine, Morgantown, WV 26506.
3WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Morgantown, WV 26506.
4Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506

Abstract

Aberrant migration of inhibitory interneurons can alter the formation of cortical circuitry and lead to severe neurologic 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.