Epigenetic regulation of neural stem cell fate during corticogenesis

► Development of NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis. ► Epigenetic modifications contribute to the regulation of NSCs fate specification during corticogenesis. ► Transcriptional repression is the central mechanism in controlling fate specification of cortical projection neurons. The cerebral cortex comprises over three quarters of the brain, and serves as structural basis for the sophisticated perceptual and cognitive functions. It develops from common multipotent neural stem cells (NSCs) that line the neural tube. Development of the NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis along with the progression of developmental stages. Interestingly, NSCs steadfastly march through all of these phases and give rise to specific neural cell types in a temporally defined and highly predictable manner. Herein, we delineate the intrinsic and extrinsic factors that dictate the progression and tempo of NSC differentiation during cerebral cortex development, and how epigenetic modifications contribute to the dynamic properties of NSCs.