SELENOT 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. SELENOT is a thioredoxin-like enzyme of the endoplasmic reticulum abundantly expressed during embryogenesis whose gene disruption in the brain leads to neuroblast cell demise due to increased free radical levels. To determine the potential contribution of SELENOT to the establishment of cortical networks, we analyzed first its expression profile in the neocortex at different stages of development. These studies revealed the widespread expression of SELENOT in all cortical layers, and its continous increase throughout mouse lifespan. In addition, we disrupted the SELENOT gene in the cortex using in utero electroporation and Nes-Cre/lox knockout. SELENOT deficiency altered neuroblast migration polarity, at the level of radial scaffolding, and projection neuron positionning. These results indicate that SELENOT plays a crucial role during neurodevelopment by sustaining projection neuron migration.