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Molecular mechanisms leading to the balance between qualitative and quantitative changes of the neural progenitor cells

Research Project

Project/Area Number 17H03684
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Sasai Noriaki  奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (80391960)

Co-Investigator(Kenkyū-buntansha) 西 晶子  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (50772422)
別所 康全  奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (70261253)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords神経管 / シグナル因子 / ソニック・ヘッジホッグ / シグナルの経時的変化 / ニワトリ胚 / 前駆細胞 / シグナル活性 / 胚性幹細胞 / 中枢神経 / 神経発生 / パターン形成 / 量的比率 / 中枢神経系 / 増殖と分化 / フィードバック効果 / 細胞増殖 / エピゲノム
Outline of Final Research Achievements

In embryonic organs, many types of cells are present with a specific amount (cell number) and pattern (relative position). This is caused by the three stages of differentiation; the cell fate determination, proliferation of progenitor cells, and time to differentiation. In this study, we analyzed temporal changes in signal activity of Sonic Hedgehog, one of the signaling molecules that control pattern formation and cell differentiation. We consequently identified a factor that controls this temporal change. In addition, in order to clarify the region-specific cell growth control mechanism, we clarified the mechanism that controls the low-proliferation of the floor plate cells. We furthermore clarified the function of the membrane protein expressed in the neural stem cells.

Academic Significance and Societal Importance of the Research Achievements

胚発生の器官発生において、様々なシグナル経路が存在することはこれまでも示されてきたが、各前駆細胞がどのようにこのシグナル因子に応答し、自身の性質を変化させるかについては不明な点が多かった。今回のプロジェクトによって、シグナル活性の経時的変化とその制御因子が明らかになったこと、また各細胞の増殖メカニズムが明らかになったことは、器官発生に関する基礎生物学的知見の蓄積ばかりでなく、再生医療に向けた基盤技術の開発、とりわけ幹細胞から作成する臓器のサイズ制御やスケーリング技術の開発に重要である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (28 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (21 results) (of which Invited: 1 results)

  • [Journal Article] Hedgehog Signal and Genetic Disorders.2019

    • Author(s)
      Sasai N, Toriyama M, Kondo T.
    • Journal Title

      Frontiers in Genetics

      Volume: 10 Pages: 1103-1103

    • DOI

      10.3389/fgene.2019.01103

    • NAID

      120006772118

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prominin-1 Modulates Rho/ROCK-Mediated Membrane Morphology and Calcium-Dependent Intracellular Chloride Flux.2019

    • Author(s)
      Hori A, Nishide K, Yasukuni Y, Haga K, Kakuta W, Ishikawa Y, Hayes MJ, Ohnuma SI, Kiyonari H, Kimura K, Kondo T, Sasai N.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 15911-15911

    • DOI

      10.1038/s41598-019-52040-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate.2019

    • Author(s)
      Kadoya M, Sasai N.
    • Journal Title

      Frontiers in Neuroscience

      Volume: 13 Pages: 1022-1022

    • DOI

      10.3389/fnins.2019.01022

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GPR17 is an essential regulator for the temporal adaptation of sonic hedgehog signalling in neural tube development.2019

    • Author(s)
      Yatsuzuka A, Hori A, Kadoya M, Matsuo-Takasaki M, Kondo T, Sasai N.
    • Journal Title

      Development

      Volume: 146

    • DOI

      10.1242/dev.176784

    • NAID

      120006718070

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GPR17 is an essential component of the negative feedback Loop of the Sonic Hedgehog signalling pathway in neural tube development2018

    • Author(s)
      Atsuki Yatsuzuka, Akiko Hori, Minori Kadoya, Mami Matsuo-Takasaki, Toru Kondo, Noriaki Sasai
    • Journal Title

      BioRxiv

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] 神経誘導2017

    • Author(s)
      笹井紀明
    • Journal Title

      脳科学辞典

      Volume: -

    • DOI

      10.14931/bsd.2114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ソニック・ヘッジホッグ2017

    • Author(s)
      笹井紀明
    • Journal Title

      脳科学辞典

      Volume: -

    • DOI

      10.14931/bsd.7348

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] CDK18はGli3のリン酸化を介してSonic Hedgehog経路を調節する2019

    • Author(s)
      西(堀)晶子, 井上亜美, 渡邊仁美, 近藤玄, 廣田圭司, 笹井紀明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Region-specific inactivation of mTOR signal and the regulation of cell proliferation2019

    • Author(s)
      Minori Kadoya, Noriaki Sasai
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 遺伝性眼疾患の原因遺伝子Prominin-1の解析2019

    • Author(s)
      渡邉静香, 小林由佳, 白井学, 木村和博, 笹井紀明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 神経管発生におけるGタンパク共役型受容体GPR17によるSonic Hedgehogシグナルへの負の制御機構2019

    • Author(s)
      八塚敦輝, 西(堀)晶子, 角谷美典, 高崎(松尾)真美, 近藤亨, 笹井紀明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Region-specific inactivation of mTOR signal and the regulation of cell proliferation2019

    • Author(s)
      Kadoya Minori, Noriaki Sasai
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Polyhomeotic homolog 1 regulates the formation of optic cup-like organoids2019

    • Author(s)
      Agnes Lee Chen Ong, Manabu Shirai and Noriaki Sasai
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規ヘリカーゼ因子ERCC6L2の神経発生における役割の解析2019

    • Author(s)
      小木曽力, 大城樹実, 笹井 紀明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト間葉系幹細胞由来神経分化型新規幹細胞の単離と神経障害治療への応用2019

    • Author(s)
      中西徹, 山崎勤, 中野敬介, 長塚仁, 杉野哲造, 笹井紀明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The G-protein coupled receptor GPR17 is an essential component of the negative feedback loop of the sonic hedgehog pathway in the neural tube development2019

    • Author(s)
      Atsuki Yatsuzuka, Akiko Hori-Nishi, Minori Kadoya, Toru Kondo and Noriaki Sasai
    • Organizer
      第52回日本発生生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GPR17 is an essential regulator for the temporal adaptation of Sonic Hedgehog signaling in neural tube development2019

    • Author(s)
      Atsuki Yatsuzuka, Akiko Hori, Minori Kadoya, Mami Matsuo-Takasaki, Toru Kondo and Noriaki Sasai
    • Organizer
      BSCB/BSDB Joint Annual Spring Meeting 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] mTORC1 signaling pathway determines the floor plate cell number during the neural tube development2019

    • Author(s)
      Minori Kadoya and Noriaki Sasai
    • Organizer
      BSCB/BSDB Joint Annual Spring Meeting 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] A Screening for the new regulatory pathway of the floor plate differentiation2018

    • Author(s)
      Minori Kadoya, Noriaki Sasai
    • Organizer
      第51回日本発生生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The Novel G-protein coupled receptor GPR17 is the Negative Feedback Loop component of the Sonic Hedgehog Pathway in the Neural Tube Development2018

    • Author(s)
      Atsuki Yatsuzuka, Akiko Hori-Nishi,, Minori Kadoya, Noriaki Sasai
    • Organizer
      第51回日本発生生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経管底板領域に発現するmTORC1の負の制御因子2018

    • Author(s)
      角谷美典、笹井紀明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Prominin-1による細胞突起形成のメカニズム2018

    • Author(s)
      堀-西 晶子、西出 賢次、近藤 亨、笹井 紀明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PRC関連遺伝子による神経前駆細胞の分化制御2018

    • Author(s)
      豊田 真奈美、白井 学、笹井 紀明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 眼疾患の原因遺伝子Prominin-1の変異細胞の作製2018

    • Author(s)
      角田 航人、堀-西 晶子、笹井 紀明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ソニック・ヘッジホッグシグナルによる細胞の増殖・分化制御メカニズム2018

    • Author(s)
      井上 亜美、堀-西 晶子、市川 朋、笹井 紀明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Induction of Cell membrane protrusions induced by Promimin-12018

    • Author(s)
      Nishi-Hori A, Nishide K, Kondo T, Sasai N.
    • Organizer
      米国細胞生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GPR17 Is an Essential Component of the Negative Feedback Loop of the Sonic Hedgehog Signalling Pathway in Neural Tube Development2018

    • Author(s)
      Yatsuzuka A, Nishi-Hori A, Kadoya M, Kondo T, Sasai N
    • Organizer
      米国細胞生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GPR17によるソニックヘッジホッグシグナルの負のフィードバック制御機構が与える神経管パターン形成への影響2017

    • Author(s)
      八塚 敦輝
    • Organizer
      ConBio 2017
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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