2023/05/19 更新

写真a

オウ セイメイ
王 晟明
O SEIMEI
担当
大学院医学研究科 基礎医科学専攻 助教
医学部 医学科
職名
助教
所属
医学研究院

担当・職階

  • 大学院医学研究科 基礎医科学専攻 

    助教  2022年10月 - 継続中

  • 医学部 医学科 

    助教  2022年10月 - 継続中

取得学位

  • 医学博士 ( 大阪市立大学 )

  • 医学学士 ( 中国医科大学 )

論文

  • Functional Cooperation of α-Synuclein and Tau Is Essential for Proper Corticogenesis

    Shengming Wang, Yu Fu, Takaki Miyata, Sakiko Matsumoto, Tomoyasu Shinoda, Kyoko Itoh, Akihiro Harada, Shinji Hirotsune and Mingyue Jin

    Journal of Neuroscience   42 ( 37 )   7031 - 7046   2022年09月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Alpha-synuclein (αSyn) and tau are abundant multifunctional neuronal proteins, and their intracellular deposits have been linked to many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Despite the disease relevance, their physiological roles remain elusive, as mice with knock-out of either of these genes do not exhibit overt phenotypes. To reveal functional cooperation, we generated αSyn−/−tau−/− double-knock-out mice and characterized the functional cross talk between these proteins during brain development. Intriguingly, deletion of αSyn and tau reduced Notch signaling and accelerated interkinetic nuclear migration of G2 phase at early embryonic stage. This significantly altered the balance between the proliferative and neurogenic divisions of progenitor cells, resulting in an overproduction of early born neurons and enhanced neurogenesis, by which the brain size was enlarged during the embryonic stage in both sexes. On the other hand, a reduction in the number of neural progenitor cells in the middle stage of corticogenesis diminished subsequent gliogenesis in the αSyn−/−tau−/− cortex. Additionally, the expansion and maturation of macroglial cells (astrocytes and oligodendrocytes) were suppressed in the αSyn−/−tau−/− postnatal brain, which in turn reduced the male αSyn−/−tau−/− brain size and cortical thickness to less than the control values. Our study identifies important functional cooperation of αSyn and tau during corticogenesis.

    DOI: https://doi.org/10.1523/JNEUROSCI.0396-22.2022

  • Lis1 mutation prevents basal radial glia-like cell production in the mouse 国際共著

    Maxime Penisson, Mingyue Jin, Shengming Wang, Shinji Hirotsune, Fiona Francis, Richard Belvindrah

    Human Molecular Genetics   35 ( 6 )   942 - 957   2022年03月

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    掲載種別:研究論文(学術雑誌)   共著区分:共著   国際・国内誌:国際誌  

    Human cerebral cortical malformations are associated with progenitor proliferation and neuronal migration abnormalities. Progenitor cells include apical radial glia, intermediate progenitors and basal (or outer) radial glia (bRGs or oRGs). bRGs are few in number in lissencephalic species (e.g. the mouse) but abundant in gyrencephalic brains. The LIS1 gene coding for a dynein regulator, is mutated in human lissencephaly, associated also in some cases with microcephaly. LIS1 was shown to be important during cell division and neuronal migration. Here, we generated bRG-like cells in the mouse embryonic brain, investigating the role of Lis1 in their formation. This was achieved by in utero electroporation of a hominoid-specific gene TBC1D3 (coding for a RAB-GAP protein) at mouse embryonic day (E) 14.5. We first confirmed that TBC1D3 expression in wild-type (WT) brain generates numerous Pax6+ bRG-like cells that are basally localized. Second, using the same approach, we assessed the formation of these cells in heterozygote Lis1 mutant brains. Our novel results show that Lis1 depletion in the forebrain from E9.5 prevented subsequent TBC1D3-induced bRG-like cell amplification. Indeed, we observe perturbation of the ventricular zone (VZ) in the mutant. Lis1 depletion altered adhesion proteins and mitotic spindle orientations at the ventricular surface and increased the proportion of abventricular mitoses. Progenitor outcome could not be further altered by TBC1D3. We conclude that disruption of Lis1/LIS1 dosage is likely to be detrimental for appropriate progenitor number and position, contributing to lissencephaly pathogenesis.

    DOI: https://doi.org/10.1093/hmg/ddab295

講演・口頭発表等

  • Functional cross-talk between α-Synuclein and tau in corticogenesis 国内会議

    Shengming Wang, Yu Fu, Takaki Miyata, Sakiko Matsumoto, Tomoyasu Shinoda, Kyoko Itoh, Akihiro Harada, Mingyue Jin, Shinji Hirotsune

    MBSJ  2022年11月 

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    会議種別:ポスター発表