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Analysis of the mechanisms underlying the layer- and region-specificity during brain development

Research Project

Project/Area Number 23500390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neuroscience in general
Research InstitutionKyoto University

Principal Investigator

OHTSUKA TOSHIYUKI  京都大学, ウイルス研究所, 准教授 (20324709)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords脳形態形成 / 神経幹細胞 / 神経発生 / 転写因子 / 発生・分化 / 脳・神経 / 神経科学 / 再生医学 / 幹細胞
Research Abstract

We analyzed the stage- and region-specific gene expression in neural stem cells during cortical development. We performed the functional analysis of Hbp1 that is highly expressed during the neurogenic stages, and found the abnormal brain morphogenesis including enlarged ventricles and thinner cortex in the Hbp1 conditional knockout mice. In the transgenic mice in which Hes1 expression is controlled by the Tet-On system, persistent high expression of Hes1 led to the maintenance of neural stem cells and the expansion of neural stem cell pool in embryonic, postnatal and adult brains. The number of Tbr2-positive intermediate progenitor cells was decreased in the cortical region, and it was found that the superficial layer is thinner and the generation of superficial layer neurons was decelerated and prolonged.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (20 results)

All 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (6 results)

  • [Journal Article] Genetic visualization of notch signaling in mammalian neurogenesis.2013

    • Author(s)
      Imayoshi I, Shimojo H, Sakamoto M, Ohtsuka T, Kageyama R
    • Journal Title

      Cell Mol Life Sci.

      Volume: 70 Issue: 12 Pages: 2045-57

    • DOI

      10.1007/s00018-012-1151-x

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hes1 and Hes5 regulate vascular remodeling and arterial specification of endothelial cells in brain vascular development.2013

    • Author(s)
      Kitagawa M, Hojo M, Imayoshi I, Goto M, Ando M, Ohtsuka T, Kageyama R, Miyamoto S.
    • Journal Title

      Mech Dev.

      Volume: 130 Issue: 9-10 Pages: 458-66

    • DOI

      10.1016/j.mod.2013.07.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accelerating the tempo of the segmentation clock by reducing the number of introns in the Hes7 gene.2013

    • Author(s)
      Harima Y, Takashima Y, Ueda Y, Ohtsuka T, Kageyama R.
    • Journal Title

      Cell Rep.

      Volume: 3 Pages: 1-7

    • NAID

      120005024759

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 発生過程の脳においてmicroRNA9 はHes1 発現動態を調節することにより神経幹細胞の分化を制御する2012

    • Author(s)
      Siok-Lay Tan, 大塚俊之, Aitor González, 影山龍一郎
    • Journal Title

      Genes Cells

      Volume: 17(12) Issue: 12 Pages: 952-961

    • DOI

      10.1111/gtc.12009

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ヒストンメチルトランスフェラーゼESET は発生過程における神経前駆細胞のエピジェネティックな制御に必須である2012

    • Author(s)
      Siok-Lay Tan, 西美幸, 大塚俊之, 他6名
    • Journal Title

      Development

      Volume: 139(20) Pages: 3806-3816

    • URL

      http://dev.biologists.org/content/139/20/3806.long

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The identification of transcriptional targets of Ascl1 in oligodendrocyte development.2012

    • Author(s)
      Ueno T, Ito J, Hoshikawa S, Ohori Y, Fujiwara S, Yamamoto S, Ohtsuka T, Kageyama R, Akai M, Nakamura K, Ogata T.
    • Journal Title

      Glia

      Volume: 60 Pages: 1495-1505

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development.2012

    • Author(s)
      Tan SL, Nishi M, Ohtsuka T, Matsui T, Takemoto K, Kamio-Miura A, Aburatani H, Shinkai Y, Kageyama R.
    • Journal Title

      Development

      Volume: 139 Pages: 3806-3816

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain.2012

    • Author(s)
      Tan SL, Ohtsuka T, Gonzalez A, Kageyama R.
    • Journal Title

      Genes Cells

      Volume: 17 Pages: 952-961

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of Hes genes in intestinal development, homeostasis and tumor formation.2012

    • Author(s)
      Ueo T, Imayoshi I, Kobayashi T, Ohtsuka T, Seno H, Nakase H, Chiba T, Kageyama R
    • Journal Title

      Development

      Volume: 139 Pages: 1071-1082

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development2011

    • Author(s)
      Ohtsuka, T., Shimojo, H., Matsunaga, M., Watanabe, N., Kometani, K., Minato, N., and Kageyama, R.
    • Journal Title

      Stem Cells

      Volume: 29 Issue: 11 Pages: 1817-1828

    • DOI

      10.1002/stem.731

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Continuous neurogenesis in the adult forebrain is required for innate olfactory responses2011

    • Author(s)
      M.Sakamoto, I.Imayoshi, T.Ohtsuka, M.Yamaguchi, K.Mori, R.Kageyama
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 108 Issue: 20 Pages: 8479-8484

    • DOI

      10.1073/pnas.1018782108

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene Expression Profiling of Neural Stem Cells and Identification of Regulators of Neural Differentiation During Cortical Development.2011

    • Author(s)
      Ohtsuka T, Shimojo H, Matsunaga M, Watanabe N, Kometani K, Minato N, Kageyama R
    • Journal Title

      Stem Cells

      Volume: 29 Pages: 1817-1828

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamic expression of notch signaling genes in neural stem/progenitor cells.2011

    • Author(s)
      Shimojo H, Ohtsuka T, Kageyama R
    • Journal Title

      Front Neurosci.

      Volume: 5 Pages: 78-78

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Continuous neurogenesis in the adult forebrain is required for innate olfactory responses.2011

    • Author(s)
      Sakamoto M, Imayoshi I, Ohtsuka T, Yamaguchi M, Mori K, Kageyama R
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 108 Pages: 8479-8484

    • NAID

      120003001324

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 神経発生過程における遺伝子発現ダイナミクスによる神経分化制御機構の解明2013

    • Author(s)
      下條博美, 播磨有希子, 前田勇樹, 大塚俊之, 他2名
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Hes1 強制発現による大脳皮質ニューロン産生遅延および生後脳における神経幹細胞の増加2013

    • Author(s)
      大塚俊之, 影山龍一郎
    • Organizer
      第5回国際幹細胞学会
    • Place of Presentation
      エルサレム, イスラエル
    • Year and Date
      2013-10-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Overexpression of Hes1 Leads to Decelerated Timing of Cortical Neurogenesis and Expansion of Neural Stem Cell Reservoir in Postnatal Brain2013

    • Author(s)
      Toshiyuki Ohtsuka, Ryoichiro Kageyama
    • Organizer
      5th International Stem Cell Meeting
    • Place of Presentation
      Jerusalem, Israel
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経発生過程における遺伝子発現ダイナミクスによる神経分化制御機構の解明2013

    • Author(s)
      下條博美、播磨有希子、前田勇樹、大塚俊之、宮地均、影山龍一郎
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経幹細胞における遺伝子発現プロファイルングおよび大脳皮質形成過程における神経分化制御因子の同定2011

    • Author(s)
      大塚俊之, 他6名
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development

    • Author(s)
      大塚俊之、下條博美、松永充博、渡邊直希、米谷耕平、湊長博、影山龍一郎
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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