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神経系の成り立ちにおける細胞の移動と上皮化

Research Project

Project/Area Number 20022028
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNara Institute of Science and Technology

Principal Investigator

高橋 淑子  Nara Institute of Science and Technology, バイオサイエンス研究科, 教授 (10183857)

Co-Investigator(Kenkyū-buntansha) 齋藤 大介  奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (90403360)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2009: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2008: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywords神経冠細胞 / 副腎 / 交感神経 / 細胞移動 / ケモカイン / BMP / CXCR4 / Neuregulin
Research Abstract

発生初期にみられる神経系組織の成立機構について、神経前駆細胞の移動と上皮化に注目し、それらを制御する分子機構の解明に取り組んだ。細胞移動については、末梢神経系のほぼすべてを作り上げる神経冠細胞(Neural crest cells;神経堤細胞ともいう。以下NCCと呼ぶ)をモデルとした解析を行い、背側大動脈からの誘引シグナルについて新規の知見を得た。また上皮形成については、第二の神経管形成であるSecondary neurulationに注目し、Pax2が重要な役割を果たすことを見いだした。まずNCCのサプタイプの1つであるSA細胞の移動機構に関して、背側大動脈がSA細胞の移動を誘引する能力をもつこと、またこの誘引能の実態が大動脈付近の間充織内で発現するケモカインSDF1とNrg1であること、さらに、SDF1とNrg1の発現は、大動脈から放出されるBMP4/7により誘導されることを明らかにした。このように、SA細胞の移動において、ターゲットとなる大動脈の重要が見えてきた。SNの機構については、SNに参画する間充織様の神経前駆細胞(予定SN細胞)を同定し、これらの細胞に特異的に遺伝子導入する系を確立した。この系を用いることで、SN形成にRhoファミリーのRac1が必要であることを明らかにした。次に、予定SN領域において転写因子Pax2が特異的に発現することに注目し、Pax2をSN領域の近傍の体節細胞内で異所的に発現させたところ、異所的な神経管構造が形成されることを発見した。この異所的なSN形成の系を利用して、Pax2はその下流で他の転写因子Tbx6L(体節中胚葉の形成に必須であることが知られている)の作用を抑制することがわかった。上記の研究から、SNによる神経管形成が、Primary Neurulationとは全く異なるメカニズムによって引き起こされることが明らかになった。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (28 results)

All 2010 2009 2008 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (13 results) Book (6 results)

  • [Journal Article] Ephrin B2 coordinates the formation of a morphological boundary and cell epithe lialization during somite segmentation.2009

    • Author(s)
      Watanabe, T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 106(18)

      Pages: 7467-7472

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Notch signal is sufficient to direct an endothelial conversion from non-endothelial somitic cells conveyed to the aortic region by CXCR4.2009

    • Author(s)
      Ohata, E.
    • Journal Title

      Developmental Biology 335

      Pages: 33-42

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A combination of transposable elements and magnetic cell sorting provides a very efficient transgenesis system for chicken primary erythrpid progenitors.2009

    • Author(s)
      Mejia-Pous, C.
    • Journal Title

      BMC Biotechnology 9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transposon-mediated stable integration and tetracycline-inducible expression of electroporated transgenes in chicken embryos2008

    • Author(s)
      Takahashi, Y.
    • Journal Title

      Methods in Cell Biology 87

      Pages: 237-256

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somitogenesis as a model to study the formation of morphological boundaries and cell epithelialization2008

    • Author(s)
      Takahashi, Y.
    • Journal Title

      Dev. Growth & Differ 50

      Pages: 149-155

    • NAID

      10024399769

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Notch mediates the segmental specification of angioblasts in somites and their directed migration toward the dorsal aorta in avian embryos2008

    • Author(s)
      Sato, Y.
    • Journal Title

      Developmental Cell 14

      Pages: 890-901

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploration of embryonic origins of germline stem cells and neoblasts in Enchytraeus japonensis2008

    • Author(s)
      Sugio, M.
    • Journal Title

      Gene Expression Patterns 8

      Pages: 227-236

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous expression of different transgenes in neurons and glia by combining in utero electroporation with Tol2 transposon mediated gene transfer system.

    • Author(s)
      Yoshida, A.
    • Journal Title

      Genes to Cells (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ephrin B2 coordinates the formation of a morphological boundary and cell epithelialization during somite segmentation

    • Author(s)
      Watanabe, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 神経提細胞をモデルとした末梢神経系の形成機構2010

    • Author(s)
      高橋淑子
    • Organizer
      第9回日本再生医療学会総会(招待講演)
    • Place of Presentation
      広島
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Vasculo-neural interactions during development.2009

    • Author(s)
      Takahashi, Y
    • Organizer
      The 32nd Annual Meeting of the Molecular Biology Society of Japan(招待講演)
    • Place of Presentation
      Yokohama
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 背側大動脈の形成を支える細胞移動とNotch-ephrinシグナル2009

    • Author(s)
      高橋淑子
    • Organizer
      第82回日本生化学会大会(招待講演)
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 血管の発生とパターニング2009

    • Author(s)
      高橋淑子
    • Organizer
      第5回Summer Vascular Conference(特別招待講演)
    • Place of Presentation
      東京
    • Year and Date
      2009-09-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cell migration during formation of blood vessels and peripheral nervous system.2009

    • Author(s)
      Takahashi, Y.
    • Organizer
      The 61st Annual Meeting of the Japan Society for Cell Biology (招待講演)
    • Place of Presentation
      Nagoya
    • Year and Date
      2009-06-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Nural crest cell migration and contribution to the adrenal glands is regulated by multiple factors mediated by CXCR4/SDF1, BMP4, and transcription factor SF-12008

    • Author(s)
      Takahashi, Y.
    • Organizer
      BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)(Symposium Organizer・特別講演)
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 器官形成における細胞挙動を制御する遺伝プログラム2008

    • Author(s)
      高橋淑子
    • Organizer
      遺伝医学セミナー(招待講演)
    • Place of Presentation
      大阪
    • Year and Date
      2008-09-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 血管発生と細胞移動2008

    • Author(s)
      高橋淑子
    • Organizer
      サントリー生物有機科学研究所(招待セミナー)
    • Place of Presentation
      大阪
    • Year and Date
      2008-06-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] 血管発生と細胞移動2008

    • Author(s)
      高橋淑子
    • Organizer
      日本分子生物学会第8回春期シンポジウム(招待講演)
    • Place of Presentation
      札幌
    • Year and Date
      2008-05-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] Transposon-mediated stable integration of genes into migrating cells during blood vessel patterning2008

    • Author(s)
      Takahashi, Y.
    • Organizer
      Experimental Biology, 2008
    • Place of Presentation
      San Diego, U. S. A.
    • Year and Date
      2008-04-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 器官形成にみる細胞の奇妙なふるまい2008

    • Author(s)
      高橋淑子
    • Organizer
      第20回 高遠・分子細胞生物学シンポジウム(招待講演)
    • Place of Presentation
      長野
    • Related Report
      2008 Annual Research Report
  • [Presentation] Neural crest cell migration to the adrenal gland is regulated by CXCR4/SDF1, BMP4, and transcription. factor SF-12008

    • Author(s)
      Takahashi, Y.
    • Organizer
      The 31st Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Secondary neurulation : a novel model to study tubulogenesis2008

    • Author(s)
      Takahashi, Y.
    • Organizer
      41th Annual Meeting for the Japanese Society of Developmental Biologists
    • Place of Presentation
      Tokushima, Japan
    • Related Report
      2008 Annual Research Report
  • [Book] 実験医学「胚体内の初期血管パターニングとガイダンス因子-Notch-ephrinシグナルが制御する細胞のふるまい」2009

    • Author(s)
      大畑絵美
    • Publisher
      羊土社
    • Related Report
      2009 Annual Research Report
  • [Book] 最新医学「幹細胞研究の最近の進歩(後編)-組織幹細胞-「発生と幹細胞:神経冠細胞の移動機構」2009

    • Author(s)
      齋藤大介
    • Publisher
      最新医学社
    • Related Report
      2009 Annual Research Report
  • [Book] 生体の医学「境界形成とEph-Ephrinシグナル」2009

    • Author(s)
      渡邉忠由
    • Publisher
      医学書院
    • Related Report
      2009 Annual Research Report
  • [Book] Electroporation and Sonoporation in Developmental Biology2009

    • Author(s)
      Ohata, E.
    • Publisher
      Springer Japan
    • Related Report
      2008 Annual Research Report
  • [Book] Electroporation and Sonoporation in Developmental Biology2009

    • Author(s)
      Sato, Y.
    • Publisher
      Springer Japan
    • Related Report
      2008 Annual Research Report
  • [Book] 細胞工学Vol.27 No.42008

    • Author(s)
      吉野剛史
    • Publisher
      秀潤社
    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-03-28  

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