A role for Hmga2 in the early-stage transition of neural stem-progenitor cell properties during mouse neocortical development

Abstract

AbstractDuring the early stage of mammalian neural development, neuroepithelial cells (NECs) proliferate and increase their pool size before switching their fate to become neurogenic radial glial cells (RGCs). The timing of this expansion-to-neurogenic phase transition is strictly regulated so as to determine the proper number of progenitors and differentiated cell types that constitute the brain. The molecular mechanism underlying this switch has remained poorly understood, however. We have now performed a transcriptomic analysis of NECs and RGCs and found that the expression of Hmga2 gene, which encodes a chromatin-associated protein, peaks at the expansion-to-neurogenic phase transition. By the use of our newly established method to manipulate NECs before neural tube closure, we found that knockdown of Hmga2 in NECs delayed the change in their transcriptomic profile and suppressed the onset of neurogenesis in the neocortex. Our study thus uncovers a key molecular player in the generation of neurogenic progenitors in the developing mouse neocortex.