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Analysis of the mechanisms underlying the maintenance/differentiation of neural stem cells and brain development/evolution in mammals

Research Project

Project/Area Number 15K06773
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKyoto University

Principal Investigator

OHTSUKA Toshiyuki  京都大学, ウイルス・再生医科学研究所, 准教授 (20324709)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords神経幹細胞 / 神経発生 / 脳発生 / 脳進化 / HES / 脳形態形成 / Hes
Outline of Final Research Achievements

We analyzed the expression and functions of human HES factors that play a central role in the maintenance of neural stem cells (NSCs) and revealed the activities of HES1/4/5 to inhibit neuronal differentiation and maintain NSCs when overexpressed. And we found that both HES1 and HES4 are expressed in the ventricular zone of brains of cynomolgus monkey embryos. The transgenic mice, in which Hes is overexpressed in NSCs of brains by using the Tet-ON system, showed a phenotype of expanded ventricles with thinner cortical plate, due to the maintenance of NSCs and inhibition of neuronal differentiation. In the Hes1-overexpressing Tg mice, basal radial glia-like cells increased in number, suggesting that the alteration in Hes expression levels contributes to the mammalian brain evolution.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development2017

    • Author(s)
      Bansod Shama、Kageyama Ryoichiro、Ohtsuka Toshiyuki
    • Journal Title

      Development

      Volume: 144 Issue: 17 Pages: 3156-3167

    • DOI

      10.1242/dev.147256

    • NAID

      120006488607

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis.2016

    • Author(s)
      Shimojo H, Isomura A, Ohtsuka T, Kori H, Miyachi H, Kageyama R
    • Journal Title

      Genes Dev.

      Volume: 30 Issue: 1 Pages: 102-116

    • DOI

      10.1101/gad.270785.115

    • NAID

      120005980896

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hbp1 regulates the timing of neuronal differentiation during cortical development by controlling cell cycle progression.2015

    • Author(s)
      Watanabe N, Kageyama R, Ohtsuka T
    • Journal Title

      Development

      Volume: 142 Pages: 2278-2290

    • DOI

      10.1242/dev.120477

    • NAID

      120006488606

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hes1 and Hes5 are required for differentiation of pituicytes and formation of the neurohypophysis in pituitary development.2015

    • Author(s)
      Goto M, Hojo M, Ando M, Kita A, Kitagawa M, Ohtsuka T, Kageyama R, Miyamoto S
    • Journal Title

      Brain Res

      Volume: 1625 Pages: 206-217

    • DOI

      10.1016/j.brainres.2015.08.045

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.2015

    • Author(s)
      Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang CL, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, Takahashi R
    • Journal Title

      PLoS Genet.

      Volume: 11 Issue: 9 Pages: e1005503-e1005503

    • DOI

      10.1371/journal.pgen.1005503

    • NAID

      120005946994

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Overexpression of Hes1 leads to prolonged neocortical neurogenesis and expansion of neural stem cell reservoir in postnatal brain2018

    • Author(s)
      Toshiyuki Ohtsuka, Ryoichiro Kageyama
    • Organizer
      The CDB Symposium 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hes5 regulates the transition timing of neurogenesis and gliogenesis in neocortical development via downregulation of Hmga genes2017

    • Author(s)
      大塚 俊之
    • Organizer
      新学術領域「脳構築における発生時計と場の連携」第1回班会議
    • Place of Presentation
      沼津 ふじのくに千本松フォーラム
    • Year and Date
      2017-01-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Hes5 regulates the transition timing of neurogenesis and gliogenesis in neocortical development via downregulation of Hmga genes2017

    • Author(s)
      大塚 俊之、Bansod Shama、影山 龍一郎
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hes genes regulate the transition timing of neurogenesis and gliogenesis in neocortical development2017

    • Author(s)
      大塚 俊之
    • Organizer
      新学術領域研究「脳構築における発生時計と場の連携」第2回領域班会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hes1強制発現により大脳皮質ニューロン産生が遷延し生後脳における神経幹細胞プールが増大する2015

    • Author(s)
      大塚俊之、影山龍一郎
    • Organizer
      第38回 日本分子生物学会年会 第88回 日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 大脳皮質形成期においてHbp1は細胞周期の長さを延長することによってニューロン分化のタイミングを制御する2015

    • Author(s)
      渡邊直希、影山龍一郎、大塚俊之
    • Organizer
      第38回 日本分子生物学会年会 第88回 日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Dynamic expression of Notch ligand Dll1 during development2015

    • Author(s)
      Hiromi Shimojo, Hiroshi Kori, Akihiro Isomura, Toshiyuki Ohtsuka, Hitoshi Miyachi, Ryoichiro Kageyama
    • Organizer
      第38回 日本分子生物学会年会 第88回 日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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