Epigenetic regulation of neural stem cell fate during corticogenesis

Abstract

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.

Mobilizing Endogenous Stem Cells for Retinal Repair

“…Epigenetic regulation includes histone modifications, DNA methylation, and other mechanisms, which work together to establish and maintain the global and local condensed or decondensed chromatin states to determine gene expression [96][97][98] . Disruption of epigenetic machineries is known to provoke aberrant gene expression patterns that give rise to developmental defect.…”

Epigenetic regulation by BAF (mSWI/SNF) chromatin remodeling complexes is indispensable for embryonic development

“…This occurs primarily via histone modification 4 or the action of ATP-dependent chromatin remodeling complexes, such as SWI/SNF (BAF) complexes. [5][6][7][8] In addition, recent studies have shown that DNA methylation 9 and long non-coding RNA (lncRNA)-based mechanisms 10 also contribute to the complexity of epigenetic regulation during development.…”

Multipotent neurogenic fate of mesenchymal stem cell is determined by Cdk4-mediated hypophosphorylation of Smad-STAT3

“…[14][15][16] Smad1/5/9 signaling actively instructs the development and differentiation of distinct neural lineages from human pluripotent stem cells and neural stem cells at the border between the epidermis and the neural plate. 15,17 In addition, differentiation into a neural lineage can be induced by the IL-6 family of cytokines [e.g., leukemia inhibitory factor (LIF) and ciliary neurotrophic factor and bone morphogenic protein (BMP) family cytokines (e.g., BMP2 and BMP4)], which activate distinct downstream transcription factors such as STAT3 and Smad1.…”

“…15,17 In addition, differentiation into a neural lineage can be induced by the IL-6 family of cytokines [e.g., leukemia inhibitory factor (LIF) and ciliary neurotrophic factor and bone morphogenic protein (BMP) family cytokines (e.g., BMP2 and BMP4)], which activate distinct downstream transcription factors such as STAT3 and Smad1. 14,16,18,19 The receptor kinases, such as TGF-b and BMP, activate Smad1 and STAT3 signaling by phosphorylation as phosphorylation plays a central role in their transcriptional activation bridged by p300. 16,20 Interestingly, the inhibition of tyrosine phosphorylation of STAT3 (at Y705 residue) is mediated by the Smad4-dependent TGF-b signaling.…”