Decoding the molecular mechanisms of neuronal migration using in utero electroporation

Abstract

During the development of the cerebral cortex, excitatory neurons are produced in the ventricular zone lining the lateral ventricle or in the adjacent subventricular zone and migrate toward the brain surface in a process known as radial migration. During radial migration, neurons undergo multiple steps including a multipolar cell phase, a multipolar-bipolar transition, and a locomotion phase. Many genes tightly regulate the cell behavior in each phase. We have established an in utero electroporation method as a rapid in vivo gene transfer system, and this system has greatly contributed to recent advances in our knowledge of the molecular mechanisms underlying each migration phase. Here, we review the cell behaviors of neurons during each phase of radial migration and the molecular mechanisms involved in these phases. Knockdown or functional blocking of these genes using in utero electroporation results in various migration defects and abnormal cell morphologies. Here, we describe these phenotypes as much as possible so that this review can be used as a chart to evaluate the phenotypes of novel gene knockdown experiments. We also discuss the recent application of in utero electroporation in studies examining the functions of neurodevelopmental disorder-related genes.

Keywords: Axon formation; Cerebral cortex; In utero electroporation; Neurodevelopmental disorders; Neuronal migration; Psychiatric disorders.