UCP2 Regulates Embryonic Neurogenesis via ROS‐Mediated Yap Alternation in the Developing Neocortex

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 oxyge...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2017-06, Vol.35 (6), p.1479-1492
Main Authors: Ji, Fen, Shen, Tianjin, Zou, Wenzheng, Jiao, Jianwei
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
Cell Cycle
Cell Cycle Proteins
Cell Differentiation
Cell Proliferation
Cellular proliferation
Degradation
Developmental biology
Differentiation
Down-Regulation
Embryo
Embryo cells
Embryogenesis
Gene Knockdown Techniques
HEK293 Cells
Humans
Mental depression
Metabolism
Mice
Mitochondria
Mitochondrial uncoupling protein 2
Models, Biological
Neocortex
Neocortex - embryology
Neocortex - metabolism
Neural stem cell
Neurogenesis
Neurons - cytology
Oxygen
Phosphoproteins - metabolism
Proteasomes
Protein Transport
Proteins
Proteolysis
Reactive oxygen species
Reactive Oxygen Species - metabolism
Rodents
Shedding
Stem cell transplantation
Stem cells
Subcellular Fractions - metabolism
Ubiquitin
Uncoupling Protein 2 - metabolism
Yes-associated protein
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Summary: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
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.2605