title: UCP2 Regulates Embryonic Neurogenesis via ROS-Mediated Yap Alternation in the Developing Neocortex.
abstract: Mitochondrial metabolism is a fundamental process in tissue development. How this process play functions in embryonic neurogenesis remains largely unknown. Here, we show that mitochondrial uncoupling protein 2 (UCP2) regulates the embryonic neurogenesis by inhibiting the production of reactive oxygen species (ROS), which affect the proliferation of progenitors. In the embryonic brains of UCP2 knockdown or condition knockout mice, the proliferation of progenitors is significantly increased, while the differentiation of progenitors is reduced. Furthermore, we identify that Yap is the response protein of UCP2-mediated ROS production. When UCP2 is inactive, the production of ROS is increased. The amount of Yap protein is increased as Yap degradation through ubiquitin-proteasome proteolytic pathway is decreased. The defect caused by UCP2 depression can be rescued by Yap downregulation. Collectively, our results demonstrate that UCP2 regulates embryonic neurogenesis through ROS-mediated Yap alternation, thus shedding new sight on mitochondrial metabolism involved in embryonic neurogenesis. Stem Cells 2017;35:1479-1492.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Fen
authors.identifier: 0000-0002-2869-103X
authors.initials: F
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Stem Cell and 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.forename: Tianjin
authors.initials: T
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.|College of Life Sciences, Qufu Normal University, Qufu, Shandong, People's Republic of China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Stem Cell and 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.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D019579:Neocortex / Q000196:embryology* / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D000071246:Uncoupling Protein 2 / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: Cellular proliferation; Developmental biology; Differentiation; Embryo; Neural stem cell