title: CHD2 is Required for Embryonic Neurogenesis in the Developing Cerebral Cortex.
abstract: Chromodomain helicase DNA-binding protein 2 (CHD2) has been associated with a broad spectrum of neurodevelopmental disorders, such as autism spectrum disorders and intellectual disability. However, it is largely unknown whether and how CHD2 is involved in brain development. Here, we demonstrate that CHD2 is predominantly expressed in Pax6(+) radial glial cells (RGs) but rarely expressed in Tbr2(+) intermediate progenitors (IPs). Importantly, the suppression of CHD2 expression inhibits the self-renewal of RGs and increases the generation of IPs and the production of neurons. CHD2 mediates these functions by directly binding to the genomic region of repressor element 1-silencing transcription factor (REST), thereby regulating the expression of REST. Furthermore, the overexpression of REST rescues the defect in neurogenesis caused by CHD2 knockdown. Taken together, these findings demonstrate an essential role of CHD2 in the maintenance of the RGs self-renewal levels, the subsequent generation of IPs, and neuronal output during neurogenesis in cerebral cortical development, suggesting that inactivation of CHD2 during neurogenesis might contribute to abnormal neurodevelopment.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Tianjin
authors: T
authors: Shen
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Fen
authors: F
authors: Ji
authors: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Zengqiang
authors: Z
authors: Yuan
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Jianwei
authors: J
authors: Jiao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology*
chemical_list: C514205:Chd2 protein, mouse; D004268:DNA-Binding Proteins
keywords: Embryonic stem cells; Neural differentiation; Neural stem cell; Progenitor cells; Proliferation; Self-renewal