SELENOPROTEIN T deficiency alters projection neuron migration during corticogenesis in mice

Abstract

During corticogenesis, projection neurons migrate along the radial glial axis to form cortical layers, the alteration of which is associated with functional deficits in adulthood. As byproducts of cell metabolism, reactive oxygen species act as second messengers to contribute to neurodevelopment; however, free radical excess may impede this process. Selenoprotein T (SELENOT) is a newly identified thioredoxin-like enzyme of the endoplasmic reticulum abundantly expressed during embryogenesis whose gene disruption in the brain leads to neuroblast cell demise and neuromorphological alterations due to increased free radical levels. To determine the potential contribution of SELENOT to the establishment of cortical networks, we first analyzed its expression profile in the neocortex at different stages of development using RNA scope in situ hybridization. These studies revealed the expression of SELENOT in different cortical layers, and its localization in glutamatergic and GABAergic neurons. Targeted SELENOT gene knockout in the cortex using in utero electroporation-mediated gene disruption or Nes-Cre/loxP transgenesis system resulted in an alteration of neuroblast migration polarity, at the level of radial scaffolding, and projection neuron positioning. These results indicate that SELENOT which is highly expressed in the cortex during neurodevelopment plays a crucial role in corticogenesis by promoting projection neuron migration.