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The female specific transcriptional regulation in murine meiosis

Research Project

Project/Area Number 20K22638
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0701:Biology at molecular to cellular levels, and related fields
Research InstitutionKumamoto University

Principal Investigator

SHIMADA Ryuki  熊本大学, 発生医学研究所, 特定事業研究員 (10882798)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords生殖細胞 / 減数分裂 / 細胞周期 / マウス / STRA8 / Rb / pre-meiotic S phase / RB / 卵細胞の休眠 / 生殖能 / scRNA-seq / 性差
Outline of Research at the Start

体細胞分裂から減数分裂への切り替えは、転写因子であるSTRA8によって制御され雌雄に共通であると考えられてきた。
我々のこれまでの研究からSTRA8が体細胞分裂を停止させる機能を持つ転写抑制因子であるRB1と結合することがわかった。さらに、STRA8のRB1との結合部位を変異させたマウスは、メスのみが不妊となることがわかった。この結果はSTRA8による減数分裂の制御機構には雌雄差があることを示唆する。
本研究では、STRA8ΔRB1メスマウスの解析からSTRA8とRB1による転写制御のメス減数分裂における意義を明らかにすることで、メス特異的な減数分裂の分子機構を解明する。

Outline of Final Research Achievements

The meiosis always start from S phase (celled pre-meiotic S phase). However, we still don't know the mechanism how meiotic initiation coincide with S phase. We revealed that the key factor of meiotic initiation, STRA8 interact with RB, which is the key suppressor of G1-S transition in canonical cell cycle, to induce pre-meiotic S phase. The regulation of pre-meiotic entry by STRA8-RB is critical for coordinated meiotic entry in female. Our study showed that STRA8-RB functions to ensure long term reproductive ability in mammalian female.

Academic Significance and Societal Importance of the Research Achievements

減数分裂開始の制御と卵細胞の分化は遺伝的に独立した機構で制御されていると考えられてきた。しかし、我々の研究成果はメス生殖細胞においてSTRA8とRBが結合することでpre-meiotic S phaseと減数分裂の開始が適切な時期に起こることが、卵細胞を性成熟期まで維持するために必要であることが明らかとなった。これはこれまでの常識を覆す重要な発見である。さらにこのSTRA8-RBによる制御はメス特異的に機能しており、減数分裂の開始機構に雌雄差があることを明確に示す結果であり、今後の研究の方向性を変え得る重要な成果である。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2022 2021

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

  • [Journal Article] FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis2022

    • Author(s)
      Tanno N, Takemoto K, Takada-Horisawa Y, Shimada R., Fujimura S, Tani N., Takeda N., Araki K, Ishiguro K
    • Journal Title

      iScience

      Volume: 25 Issue: 4 Pages: 104008-104008

    • DOI

      10.1016/j.isci.2022.104008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis2021

    • Author(s)
      Horisawa-Takada Yuki et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3184-3184

    • DOI

      10.1038/s41467-021-23378-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] STRA8-RB interaction coordinates S phase entry and meiotic initiation in female germ cells2022

    • Author(s)
      Ryuki Shimada
    • Organizer
      55th Annual Meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2021 Annual Research Report
  • [Presentation] RB-STRA8 interaction coordinates the S phase entry and meiotic initiation in mouse female germ cells2021

    • Author(s)
      Ryuki Shimada
    • Organizer
      PDSM2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] STRA8 plays multiple roles in gonadal germ cell development and meiotic cell cycle in mouse female2021

    • Author(s)
      Ryuki Shimada
    • Organizer
      International Symposium on the Biology of Vertebrate Sex determinaiton
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RB-STRA8 interaction coordinates the S phase entry and meiotic initiation in mouse female germ cells2021

    • Author(s)
      島田龍輝
    • Organizer
      PDSM2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 減数分裂誘導因子STRA8と細胞制御因子RBの結合による減数分裂の開始と卵母細胞の維持2021

    • Author(s)
      島田龍輝
    • Organizer
      新学術領域 全能性エピゲノム&非ゲノム複製 合同若手勉強会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2025-03-27  

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