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細胞集団の自律性を司る競合的コミュニケーションと互恵的コミュニケーションの連携

Publicly Offered Research

Project AreaUnderstanding multicellular autonomy by competitive cell-cell communications
Project/Area Number 22H05642
Research Category

Grant-in-Aid for Transformative Research Areas (A)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionNational Institutes of Natural Sciences

Principal Investigator

高田 慎治  大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 教授 (60206753)

Project Period (FY) 2022-06-16 – 2024-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords遺伝子 / 細胞 / 発生・分化 / シグナル伝達
Outline of Research at the Start

研究代表者のこれまでの研究ならびに他の先行研究から、集団内のWntの不均一性は細胞競合により最終的には解消されるものの、その前段階としてWntリガンドの相互交換によりWntシグナルの格差の拡大を防ぐ仕組みがあり、この両者が重層的に機能することによって細胞集団の大きさと質が最適化されることが推察される。そこで本研究では、Wntリガンド交換による互恵的な細胞間コミュニケーションと細胞競合による競合的コミュニケーションが如何に連携しながら細胞集団を最適化するのかを理解することを目指す。

Outline of Annual Research Achievements

集団内の不均一性は細胞競合により解消される。しかしながら、研究代表者のこれまでの研究により、マウス胚の後端に位置する神経中胚葉前駆細胞集団においては、その前段階としてWntリガンドの相互交換によりWntシグナルの格差をできるだけ拡大させない仕組みがあり、この両者が重層的に機能することによって細胞集団の大きさと質が最適化されるという可能性が強く示唆される。本研究ではこの仮説を検証するために、Wntリガンドの相互交換すなわちパラクリンシグナルのみが欠失したWnt3aノックインホモ個体胚を用いた。この胚では、神経中胚葉前駆細胞集団内におけるWntシグナルレベルの不均一性が拡大するが、活性化カスパーゼ3抗体による免疫組織染色等により検出できるアポトーシスも亢進していた。このことから、Wntシグナルレベルの不均一性の拡大が細胞競合の出現頻度を高めていることが示唆された。
本研究では同時に、神経中胚葉前駆細胞集団だけでなく、同様なWntリガンドが発現する神経管背側領域におけるWntリガンドの相互交換の意義についても検討した。神経管ではWnt1とWnt3aが機能的に補完しあうことから、パラクリンシグナルのみが欠失したWnt3aノックインホモ個体胚にWnt1変異導入したマウス胚を作成し、神経管の発生を詳細に検討した。当初の想定に反し、Wnt1/3aノックインホモ個体胚の表現型解析により、Wntによる制御が従来のモデルとは異なる機構で行われていることが示唆された。現在、その詳細についての解析を進めている。

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

神経管におけるパラクライン欠失Wntマウスの解析から、従来の定説とは異なるWntの作用機構が示唆された。この結果は当初の予想を超えた新しい発見につながる可能性を示唆しており、本研究は当初の計画以上に進展していると考えられる。

Strategy for Future Research Activity

神経管の解析において従来の定説を覆すWntの作用モデルが示唆されたことから、その実証に向けた研究を進めていく。

Report

(1 results)
  • 2022 Annual Research Report
  • Research Products

    (17 results)

All 2024 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 10 results,  Invited: 2 results)

  • [Int'l Joint Research] エクスター大学(英国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Soluble Frizzled-related proteins promote exosome-mediated Wnt re-secretion2024

    • Author(s)
      Tran Thi Hong Nguyen、Takada Ritsuko、Krayukhina Elena、Maruno Takahiro、Mii Yusuke、Uchiyama Susumu、Takada Shinji
    • Journal Title

      Communications Biology

      Volume: 7 Issue: 1 Pages: 254-254

    • DOI

      10.1038/s42003-024-05881-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dissection of N‐deacetylase and N‐sulfotransferase activities of NDST1 and their effects on Wnt8 distribution and signaling in Xenopus embryos2024

    • Author(s)
      Suzuki Minako、Takada Shinji、Mii Yusuke
    • Journal Title

      Development, Growth & Differentiation

      Volume: 68 Issue: 3 Pages: 248-255

    • DOI

      10.1111/dgd.12915

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis2023

    • Author(s)
      Yudai Hatakeyama, Nen Saito, Yusuke Mii, Ritsuko Takada, Takuma Shinozuka, Tatsuya Takemoto, Naoki Honda & Shinji Takada
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-023-37350-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ripply suppresses Tbx6 to induce dynamic-to-static conversion in somite segmentation2023

    • Author(s)
      Yabe Taijiro、Uriu Koichiro、Takada Shinji
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 2115-2115

    • DOI

      10.1038/s41467-023-37745-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Axonal transport of Frizzled5 by Alcadein α-containing vesicles is associated with kinesin-12023

    • Author(s)
      Shiraki Yuzuha、Mitsuma Monet、Takada Ritsuko、Hata Saori、Kitamura Akira、Takada Shinji、Kinjo Masataka、Taru Hidenori、M?ller Ulrike C.、Yamamoto Tohru、Sobu Yuriko、Suzuki Toshiharu
    • Journal Title

      Molecular Biology of the Cell

      Volume: 34 Issue: 11

    • DOI

      10.1091/mbc.e22-10-0495

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos2023

    • Author(s)
      Shinozuka Takuma、Aoki Motoko、Hatakeyama Yudai、Sasai Noriaki、Okamoto Hitoshi、Takada Shinji
    • Journal Title

      Developmental Dynamics

      Volume: 253 Issue: 4 Pages: 435-446

    • DOI

      10.1002/dvdy.659

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Intercellular exchange of Wnt ligands reduces cell population heterogeneity during embryogenesis2023

    • Author(s)
      S. Takada
    • Organizer
      Wnt Signaling, Gordon Research Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Significance of intercellular exchange of Wnt ligands in embryogenesis2023

    • Author(s)
      S. Takada
    • Organizer
      Wnt signaling seminer series supported by the German Research Foundation (DFG; CRC1324)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mutual regulation among Wnt11 and core PCP components is involved in self-organization of planar cell polarity.2023

    • Author(s)
      Yusuke Mii, Minako Suzuki, Hiroshi Koyama, Ritsuko Takada, Makoto Matsuyama, Toshihiko Fujimori, Shinji Takada
    • Organizer
      Wnt Signaling, Gordon Research Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Soluble Frizzled-related proteins promote exosome-mediated Wnt re-secretion2023

    • Author(s)
      Thi Hong Nguyen Tran, Ritsuko Takada,Elena Krayukhina, Takahiro Maruno, Yusuke Mii, Susumu Uchiyama, and Shinji Takada
    • Organizer
      Wnt Signaling, Gordon Research Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Different modification states of heparan sulfate proteoglycans are differently involved in spatial distribution of Wnt11 and in feedback regulation of planar cell polarity2022

    • Author(s)
      M. Suzuki, S. Takada, Y. Mii
    • Organizer
      EMBO Workshop Wnt 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Wnt gradient formation by dynamic exchange of abundant heparan sulfate-bound and rare freely diffusing ligands2022

    • Author(s)
      Y Mii, K Nakazato, C-G Pack, T Ikeda, Y Sako, A Mochizuki, M Taira, S Takada
    • Organizer
      EMBO Workshop Long-distance cell-cell signalling in development and disease
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exosome-mediated secretion of Wnt3a is promoted by Wnt-binding protein sFRP22022

    • Author(s)
      TH Nguyen Tran, S. Takada, S. Uchiyama, R. Takada
    • Organizer
      EMBO Workshop Wnt 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quantitative analysis of diffusing population of endogenous Wnt8 protein in zebrafish2022

    • Author(s)
      Yabe T., Mii Y. and Takada S.
    • Organizer
      EMBO Workshop Wnt 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mutual regulations between Wnt11 and core PCP components establish planar cell polarity.2022

    • Author(s)
      Y Mii, M Suzuki, H Koyama, R Takada, M Matsuyama, T Fujimori, S Takada
    • Organizer
      EMBO Workshop Wnt 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of paracrine Wnt signaling in body axis elongation of mouse embryos2022

    • Author(s)
      S. Takada
    • Organizer
      The 68th NIBB Conference "Principles of cell communiction in the tissue
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2022-06-20   Modified: 2024-12-25  

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