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Intercellular communications in embryos that recognizes Hippo signaling of the neighboring cells

Research Project

Project/Area Number 17H03682
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionOsaka University

Principal Investigator

Sasaki Hiroshi  大阪大学, 生命機能研究科, 教授 (10211939)

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: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords細胞競合 / エピブラスト / 多能性細胞 / 着床前胚 / マウス胚 / 品質管理 / Hippoシグナル / 細胞分化 / 品質管理機構 / 細胞間コミュニケーション / マウス初期胚 / 胚葉形成・原腸形成
Outline of Final Research Achievements

Correctness is an important feature of development. In developing embryos, however, behaviors and states of individual cells are highly variable. Thus, it has been a question how embryos achieve correct development by overcoming developmental variations/fluctuations. In this study, we have found that during formation of pluripotent epiblast cells in preimplantation mouse embryos, variations in Hippo signaling cause variable expression of pluripotency factors among cells, and that a quality control mechanism, which eliminates the low-quality/low pluripotency factor cells by apoptosis through short-range inter-cellular communication known as cell competition, is present. We propose that this is a mechanism, which overcomes variations during cell differentiation and supports correct developmen.

Academic Significance and Societal Importance of the Research Achievements

私たちの体を作る発生という現象の正確性がなぜ担保されるのか、というのは大きな疑問であったが、本研究の成果は、細胞競合という隣接間の細胞間のコミュニケーションが、発生が内包する細胞分化過程の揺らぎを乗り越えて、正確な発生を可能にする一つの仕組みであることを、世界に先駆けて示したものであり、発生学の分野における重要な研究成果である。また、本研究は多能性細胞の品質管理機構が存在することを示したものであり、その仕組みを応用することにより、iPS細胞などの多能性細胞の品質管理機構の開発につながる可能性がある。

Report

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

    (14 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 7 results) Remarks (1 results)

  • [Journal Article] Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells.2019

    • Author(s)
      Hashimoto M, Sasaki H.
    • Journal Title

      Dev Cell

      Volume: 50 Issue: 2 Pages: 139-154

    • DOI

      10.1016/j.devcel.2019.05.024

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obesity in Yap transgenic mice is associated with TAZ downregulation2018

    • Author(s)
      Kamura Keiichiro、Shin Jihoon、Kiyonari Hiroshi、Abe Takaya、Shioi Go、Fukuhara Atsunori、Sasaki Hiroshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 505 Issue: 3 Pages: 951-957

    • DOI

      10.1016/j.bbrc.2018.10.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neural progenitor cells undergoing Yap/Tead-mediated enhanced self-renewal form heterotopias more easily in the diencephalon than in the telencephalon.2018

    • Author(s)
      K.Saito, R. Kawasoe, H. Sasaki, A. Kawaguchi and T. Miyata
    • Journal Title

      Neurochem Res

      Volume: 43 Issue: 1 Pages: 171-180

    • DOI

      10.1007/s11064-017-2390-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Epiblast formation by Tead-Yap-dependent expression of pluripotency factors and competitive elimination of unspecified cells2019

    • Author(s)
      Masakazu Hashimoto, Hiroshi Sasaki
    • Organizer
      第52回日本発生生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mechanisms of epiblast formation during preimplantation mouse embryos2019

    • Author(s)
      Hiroshi Sasaki
    • Organizer
      TEMTIA-IX (The 9th EMT International Association Meeting)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Hippoシグナルと細胞競合によるエピブラスト形成2019

    • Author(s)
      佐々木 洋
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Epiblast formation by Tead-Yap-dependent expression of pluripotency factors and competitive elimination of unspecified cells2019

    • Author(s)
      Masakazu Hashimoto, Hiroshi Sasaki
    • Organizer
      Keystone symposia: Cell competition in Development and Disease
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tead transcription factors control pluripotency and cell competition during formation of epiblast2018

    • Author(s)
      Hiroshi Sasaki
    • Organizer
      117th International Titisee Conference: From oocyte to embryo – illuminating the origins of life
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞競合による多能性細胞形成時の品質管理2018

    • Author(s)
      佐々木 洋
    • Organizer
      第5回 細胞生物学信州夏期セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウス胚エピブラスト形成時のHippoシグナルと細胞競合の役割2018

    • Author(s)
      佐々木 洋
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Tead activity controls cell competition around implantation stage2017

    • Author(s)
      Sasaki, Hiroshi
    • Organizer
      3rd Cell Competition International Symposium: Cell Competition in Development and Cancer
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tead activity-triggered cell competition as a safeguard during establishment of epiblast in mouse embryos2017

    • Author(s)
      Sasaki, Hiroshi
    • Organizer
      EMBO workshop on the Hippo pathway across species and disciplines
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tead活性の違いによる細胞競合がマウスの初期胚発生にはたす役割2017

    • Author(s)
      佐々木 洋
    • Organizer
      生命科学系学会合同年次大会 ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] 着床前胚での細胞同士のコミュニケーションで高品質に!?

    • URL

      http://www.fbs.osaka-u.ac.jp/jpn/events/achievement/sasaki-20190613/

    • Related Report
      2019 Annual Research Report

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

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