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Are astrocytes multifunctional or classified into diverse lineages?

Research Project

Project/Area Number 20300129
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKumamoto University

Principal Investigator

KAGAWA Tetsushi  Kumamoto University, 難治疾患研究所, 准教授 (50270484)

Co-Investigator(Renkei-kenkyūsha) KASHIWAGI Taichi  東京医科歯科大学, 難治疾患研究所, 特任助教 (10398232)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsグリア細胞 / シナプス形成 / 神経回路網 / 発生 / アストロサイト
Research Abstract

In the vertebrate central nervous system (CNS), astrocytes perform multiple functions to support neural activities: including provision of neutrients to neurons, recycling of neurotransmitters and formation of blood brain barrier. In addition to their classical roles, recent studies have demonstrated that glial cells are widely involved in the regulation of synaptogenesis and synaptic activities. However, it has been poorly understood whether astrocytes can be classified into widely divergent cell lineages with their specific functions. If so, the mechanisms and timing of astrocyte sub-lineage commitments are interesting subjects. Alternatively, astrocytes may be a homogeneous cell population and adopt to change their functions according to their local environment. To challenge this question, we established a GFAP/Cre-reporter mouse line that carries the "loxP-nlacZ-loxP-GAP43GFP" cassette in glial fibrillary acidic protein (GFAP) gene locus. In this mouse CNS, only a sub-lineage of astrocytes, whose ancestral progenitor cells express cre recombinase, express GAP43GFP. As a first step, the GFAP/loxP-reporter mice were crossbred with Emx1-Cre KI Δneo mice (provided by Drs. Iwasato and Itohara) to label Emx1-positive pallial progenitors-derived astorocytes as GFP+ cells. Most astrocytes in cortical plate were βGal-/GFP+, while a subpopulation of midline glia that guided corpus callosum formation were βGal+/GFP-, suggesting that functionally different cortical astrocytes and midline glia were generated from different origins. To further investigate unique functions, if any, for the cortical and hippocampal GFAP+ cells, they were isolated using cell sorter and subjected for gene expression microarray analysis. Hippocampal GFAP+ cells expressed several genes characteristic of neural progenitor cells and immature neurons.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (47 results)

All 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 3 results) Presentation (31 results) Book (2 results) Remarks (3 results)

  • [Journal Article] 2010 Wnt3a Promotes Hippocampal Neurogenesis by Shortening Cell Cycle Duration of Neural Progenitor Cells.2010

    • Author(s)
      Yoshinaga Y, Kagawa T, Shimizu T, Inoue T, Takada S, Kuratsu J, Taga T
    • Journal Title

      Cell Mol Neurobiol. 30(7)(Epub 2010 Jun 30)

      Pages: 1049-58

    • Related Report
      2010 Final Research Report
  • [Journal Article] Involvement of the Hipk family in regulation of eyeball size, lens formation and retinal morphogenesis.2010

    • Author(s)
      Inoue T, Kagawa T, Inoue-Mochita M, Isono K, Ohtsu N, Nobuhisa I, Fukushima M, Tanihara H, Taga T
    • Journal Title

      FEBS Letters. Jul 16 584(14)(Epub 2010 Jun 19)

      Pages: 3233-8

    • Related Report
      2010 Final Research Report
  • [Journal Article] Wnt・FGF・Notchシグナル相互作用による神経幹細胞自己複製の制御機構2010

    • Author(s)
      鹿川哲史、田賀哲也
    • Journal Title

      医学のあゆみ 233:10

      Pages: 1032-1036

    • Related Report
      2010 Final Research Report
  • [Journal Article] 癌幹細胞の自己複製へのアプローチ2010

    • Author(s)
      椨康一、鹿川哲史、田賀哲也
    • Journal Title

      実験医学 28:4

      Pages: 517-524

    • Related Report
      2010 Final Research Report
  • [Journal Article] Wnt3a Promotes Hippocampal Neurogenesis by Shortening Cell Cycle Duration of Neural Progenitor Cells.2010

    • Author(s)
      吉永豊、鹿川哲史, 他
    • Journal Title

      Cellular and Molecular Neurobiology

      Volume: 30 Pages: 1049-1058

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the Hipk family in regulation of eyeball size, lens formation and retinal morphogenesis.2010

    • Author(s)
      井上俊洋、鹿川哲史, 他
    • Journal Title

      FEBS Letters

      Volume: 584 Pages: 3233-3238

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌幹細胞の自己複製へのアプローチ2010

    • Author(s)
      椨康一、鹿川哲史、田賀哲也
    • Journal Title

      実験医学 28

      Pages: 517-524

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 幹細胞の挙動追跡のための子宮内胎仔への遺伝子導入法2009

    • Author(s)
      鹿川哲史
    • Journal Title

      再生医療 8:3

      Pages: 335-340

    • Related Report
      2010 Final Research Report
  • [Journal Article] 幹細胞の挙動追跡のための子宮内胎仔への遺伝子導入法2009

    • Author(s)
      鹿川哲史
    • Journal Title

      再生医療 8

      Pages: 335-340

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Stabilized b-Catenin Functions through TCF/LEF Proteins and the Notch/RBP-Jκ Complex To Promote Proliferation and Suppress Differentiation of Neural Precursor Cells.2008

    • Author(s)
      Shimizu T, Kagawa T, Inoue T, Nonaka A, Takada S, Aburatani H, Taga T
    • Journal Title

      Mol Cell Biol. 28(24)

      Pages: 7427-7441

    • Related Report
      2010 Final Research Report
  • [Journal Article] Stabilized beta-Catenin Functions through TCF/LEF Proteins and the Notch/RBP-Jkappa Complex To Promote Proliferation and Suppress Differentiation of Neural Precursor Cells2008

    • Author(s)
      Shimizu, T., et al.
    • Journal Title

      MOLECULAR AND CELLULAR BIOLOGY 28

      Pages: 7427-7441

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 中枢神経系グリア亜集団細胞系譜のGFAP/Creレポーターマウスを用いた解析2010

    • Author(s)
      鹿川哲史, 他
    • Organizer
      Neuro2010
    • Place of Presentation
      兵庫県、神戸コンベンションセンター
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経幹細胞/前駆細胞における細胞周期調節因子cyclin D 1のアストロサイト分化抑制機構2010

    • Author(s)
      備前典久, 他
    • Organizer
      Neuro2010
    • Place of Presentation
      兵庫県、神戸コンベンションセンター
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 中枢神経系グリア亜集団細胞系譜の発生起源解析2010

    • Author(s)
      鹿川哲史、田賀哲也
    • Organizer
      第115回日本解 剖学会総会・全国学術集会、シンポジウム発表
    • Place of Presentation
      岩手、岩手県民会館
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 中枢神経系グリア亜集団細胞系譜の発生起源解析2010

    • Author(s)
      鹿川哲史、田賀哲也
    • Organizer
      第115回日本解剖学会総会・全国学術集会
    • Place of Presentation
      岩手
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Analysis of glial cell sub-lineages in the developing central nervous system using GFAP/Cre-reporter mouse system中枢神経系グリア亜集団細胞系譜のGFAP/Creレポーターマウスを用いた解析2010

    • Author(s)
      Tetsushi Kagawa, Takeshi Shimizu, Kimi Araki, Naoki Takeda, Naomi Nakagata, Ikuo Nobuhisa, Tetsuya Taga
    • Organizer
      Neuro 2010
    • Place of Presentation
      兵庫、神戸コンベンションセンター
    • Related Report
      2010 Final Research Report
  • [Presentation] Cyclin D1 inhibits astrocyte differentiation from neural stem/progenitor cells in a manner independent of cell cycle progression.2010

    • Author(s)
      備前典久, 井上俊洋, 清水健史, 鹿川哲史, 田賀哲也
    • Organizer
      第33回日本分子生物学会年会第83回日本生 化学会大会合同大会
    • Place of Presentation
      兵庫、神戸コンベンションセンター
    • Related Report
      2010 Final Research Report
  • [Presentation] Gene expression and functional analyses of histone demethylase Gasc1 in brain.2010

    • Author(s)
      Yasuhiro Kokubu, Yuhei Yamaguchi, Satoko Hattori, Keizo Takao, Joji Inazawa, Tsuyoshi Miyakawa, Tetsushi Kagawa, Tetsuya Taga
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学会大会合同大会
    • Place of Presentation
      兵庫、神戸コンベンションセンター
    • Related Report
      2010 Final Research Report
  • [Presentation] 神経幹細胞/前駆細胞における細胞周期調節因子cyclin D1のアストロサイト分化抑制機構 Molecular mechanism underlying cyclin D1 mediated inhibition of astrocyte differentiation from neural stem/progenitor cells.2010

    • Author(s)
      備前典久、井上俊洋、清水健史、鹿川哲史、田賀哲也
    • Organizer
      Neuro 2010
    • Place of Presentation
      兵庫、神戸コンベンションセンター
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular mechanism underlying cyclin D1 mediated inhibition of astrocyte differentiation from neural stem/progenitor cells.2010

    • Author(s)
      備前典久, 井上俊洋, 清水健史, 鹿川哲史, 田賀哲也
    • Organizer
      第8回幹細胞シンポジウム
    • Place of Presentation
      兵庫、淡路夢舞台国際会議場
    • Related Report
      2010 Final Research Report
  • [Presentation] 神経幹細胞前駆細胞における細胞周期調節因子Cyclin D1のアストロサイト分化抑制機構2010

    • Author(s)
      備前典久、井上俊洋、清水健史、鹿川哲史、田賀哲也
    • Organizer
      経発生討論会
    • Place of Presentation
      愛知、岡崎カンファレンスセンター
    • Related Report
      2010 Final Research Report
  • [Presentation] Cyclin D 1 inhibits astrocyte differentiation from neural stem/progenitor cells in a manner independent of cell cycle progression.2010

    • Author(s)
      備前典久, 他
    • Organizer
      第33回日本分子生物学会年会 第83回日本生化学会大会合同大会
    • Place of Presentation
      兵庫県、神戸コンベンションセンター
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene expression and functional analyses of histone demethylase Gascl in brain.2010

    • Author(s)
      国分康博, 他
    • Organizer
      第33回日本分子生物学会年会 第83回日本生化学会大会合同大会
    • Place of Presentation
      兵庫県、神戸コンベンションセンター
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanism underlying cyclin D 1 mediated inhibition of astrocyte differentiation from neural stem/progenitor cells.2010

    • Author(s)
      備前典久, 他
    • Organizer
      第8回幹細胞シンポジウム
    • Related Report
      2010 Annual Research Report
  • [Presentation] FGF signaling inhibitor Sprouty 4 contributes to neural stem cell proliferation and fate determination.2009

    • Author(s)
      Taichi Kashiwagi, Tetsushi Kagawa, Tetsuya Taga
    • Organizer
      The 32nd Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      2009-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] FGF signaling inhibitor Sprouty 4 contributes to neural stem cell proliferation and fate determination.2009

    • Author(s)
      Taichi Kashiwagi, 鹿川哲史, 田賀哲也
    • Organizer
      第32回分子生物学会
    • Place of Presentation
      神奈川
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 中枢神経系グリア細胞亜集団の細胞系譜解析2009

    • Author(s)
      鹿川哲史、田賀哲也
    • Organizer
      第52回日本神経化学会大会、シンポジウム発表
    • Place of Presentation
      群馬、伊香保温泉ホテル天坊
    • Year and Date
      2009-06-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 中枢神経系グリア細胞亜集団の細胞系譜解析2009

    • Author(s)
      鹿川哲史、田賀哲也
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      群馬
    • Year and Date
      2009-06-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Studies on FGF2 Signaling in Neural Precursor Cells. Myelin Development, Function and Related Diseases2009

    • Author(s)
      鹿川哲史, 清水健史, 田賀哲也
    • Organizer
      9^<th> Biennial Satellite Meeting of International Society for Neurochemistry on Myelin Biology
    • Place of Presentation
      TEMF Hotel, Gyeongju, Korea
    • Related Report
      2010 Final Research Report
  • [Presentation] 神経幹細胞画分における細胞周期調節因子cyclin D1は細胞周期調節非依存的にアストロサイト分化を阻害する2009

    • Author(s)
      備前典久、井上俊洋、清水健史、鹿川哲史、田賀哲也
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      伊香保、ホテル天坊
    • Related Report
      2010 Final Research Report
  • [Presentation] Cyclin D1 inhibits astrocyte differentiation from neural stem/progenitor cells in a manner independent of cell cycle regulation.2009

    • Author(s)
      備前典久, 井上俊洋, 清水健史, 鹿川哲史, 田賀哲也
    • Organizer
      The 7^<th> Stem Cell Research Symposium
    • Place of Presentation
      Izumi Garden Gallery, Tokyo
    • Related Report
      2010 Final Research Report
  • [Presentation] tudies on FGF2 Signaling in Neural Precursor Cells. Myelin Development, Function and Related Diseases2009

    • Author(s)
      鹿川哲史, 清水健史, 田賀哲也
    • Organizer
      9^<th> Biennial Satellite Meeting of International Society for Neurochemistry on Myelin Biology
    • Place of Presentation
      Gyeongju, Korea
    • Related Report
      2009 Annual Research Report
  • [Presentation] 経幹細胞画分における細胞周期調節因子cyclin D1は細胞周期調節非依存的にアストロサイト分化を阻害する2009

    • Author(s)
      備前典久、井上俊洋、清水健史、鹿川哲史、田賀哲也
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      群馬
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cyclin D1 inhibits astrocyte differentiation from neural stem/progenitor cells in a manner independent of cell cycle regulation.2009

    • Author(s)
      Bizen, N., 井上俊洋, 清水健史, 鹿川哲史, 田賀哲也
    • Organizer
      The 7^<th> Stem Cell Research Symposium
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] 中枢神経系グリア細胞亜集団の発生起源解析2008

    • Author(s)
      鹿川哲史、清水健史、荒木喜美、竹田直樹、田賀哲也
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京、シェーンバッハサボー
    • Year and Date
      2008-11-08
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス中枢神経系クリア細胞亜集団の発生起源解析2008

    • Author(s)
      鹿川哲史, ほか
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京 シェーンバッハサボー
    • Year and Date
      2008-11-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] Cyclin Dl inhibits astrocyte differentiation in the section of neural stem cell.2008

    • Author(s)
      備前典久, ほか
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山市 富山国際会議場
    • Year and Date
      2008-09-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] Establishment of GFAP/Cre-reporter mouse system to analyze glial cell sub-lineages in the developing central nervous system.2008

    • Author(s)
      鹿川哲史, ほか
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山市 富山国際会議場
    • Year and Date
      2008-09-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス中枢神経系グリア細胞系譜の解析2008

    • Author(s)
      鹿川哲史、清水健史、荒木喜美、竹田直樹、田賀哲也
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山、富山国際会議場
    • Related Report
      2010 Final Research Report
  • [Presentation] 神経幹細胞画分における細胞周期調節因子cyclin D1はアストロサイト分化を阻害する2008

    • Author(s)
      備前典久、井上俊洋、清水健史、鹿川哲史、田賀哲也
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山、富山国際会議場
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of glial cell sub-lineages in the developing mouse central nervous system.2008

    • Author(s)
      鹿川哲史、荒木喜美、竹田直樹、清水健史、田賀哲也
    • Organizer
      中枢神経系グリア細胞亜集団の発生起源解析第41回日本発生生物学会大会
    • Place of Presentation
      徳島、徳島産業文化会館
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of glial cell sub-lineages in the developing mouse central nervous system.2008

    • Author(s)
      鹿川哲史, ほか
    • Organizer
      第41回日本発生生物学会大会
    • Place of Presentation
      徳島市 徳島県郷土文化会館
    • Related Report
      2008 Annual Research Report
  • [Book] 福田信治神経系の分化、形成、再生、改訂第3版分子生物学イラストレイテッド2009

    • Author(s)
      田賀哲也、鹿川哲史、清水健史
    • Related Report
      2010 Final Research Report
  • [Book] 改訂第3版 分子生物学イラストレイテッド2008

    • Author(s)
      田賀哲也, ほか著
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.tmd.ac.jp/mri/scr/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://ww.tmd.ac.jp/mri/scr/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/mri/b_1.html#7

    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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