Abstract
During 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 progenitors (RGPs). 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, in part because of the difficulty associated with manipulation of gene expression in NECs before their transition to RGPs, which occurs before neural tube closure. We have now developed a simple and efficient method to manipulate gene expression in mouse neocortical NECs in the expansion phase by in utero injection of viral vectors at embryonic day 7.0 to 8.0. With the use of this method, we found that knockdown of the chromatin-associated protein Hmga2 in NECs inhibited the onset of the neurogenic phase in the neocortex. This effect of Hmga2 knockdown was accompanied by inhibition of the expression of a set of genes targeted by Polycomb group proteins, which repress neurogenic genes in cortical progenitors. Our study thus establishes a novel method for manipulation of gene expression in the early stage of mouse brain development as well as uncovers a key molecular player in the generation of neurogenic progenitors in the developing mouse neocortex.
Competing Interest Statement
The authors have declared no competing interest.
