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Investigation of the inhibitory mechanisms for circadian clock ossillation during early development of mammals

Research Project

Project/Area Number 19K06679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Umemura Yasuhiro  京都府立医科大学, 医学(系)研究科(研究院), 講師 (40612734)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords体内時計 / 体節時計 / 概日時計 / 個体発生 / 概日リズム
Outline of Research at the Start

哺乳類の個体発生における体内時計は、胎児期より徐々に形成されてくることが知られている。母子同調が起きていると考えられるため、胎児の体内時計に関しては、これまで重要だとは思われてこなかった。ところが、最近、申請者は個体発生過程のある時期までは、胚の概日時計がいくつもの機構で抑制されており、母体の概日リズムからさえも遮蔽されていることを見出した(Umemura et al., PNAS, 2017)。本研究では、さらに、この研究を推進し、「発生過程における体内時計の抑制機構の全容解明」を目指す。

Outline of Final Research Achievements

Although it has been reported that there are several mechanisms to inhibit the circadian clock oscillation such as the post-transcriptional suppression of CLOCK protein during mouse early development, the biological significance is unknown. In the present study, we reported that the premature expression of functional CLOCK/BMAL1, circadian clock core transcriptional factors, may affect the Hes7 gene expression oscillations and the somitogenesis process via the signaling pathways regulating the Hes7 expressions. These results suggested that the suppression of circadian clock oscillation during early development may be caused by preventing the CLOCK/BMAL1 from interfering with the normal somitogenesis process.

Academic Significance and Societal Importance of the Research Achievements

生命は、どのように「時間」を内包して進化してきたのか。これまでに、概日時計と体節時計という2つのリズム制御機構が存在することが知られていた。リズムを刻むということは、同時に、そこに時間が流れていることを意味する。これら2つの時計は、個体発生過程において相互排他的に存在しているのであるが、その意義については不明であった。本研究により、これらの2つのリズム制御機構が干渉しうるということが示唆され、生命が時間を内包する原理を明らかにする手がかりとなる可能性があり、時間生物学的な意義は大きいと考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results)

  • [Journal Article] Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids2021

    • Author(s)
      Umemura Yasuhiro、Koike Nobuya、Tsuchiya Yoshiki、Watanabe Hitomi、Kondoh Gen、Kageyama Ryoichiro、Yagita Kazuhiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 1

    • DOI

      10.1073/pnas.2114083119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circadian clock and cancer: From a viewpoint of cellular differentiation2020

    • Author(s)
      Tsuchiya Yoshiki, Umemura Yasuhiro, Yagita Kazuhiro
    • Journal Title

      International Journal of Urology

      Volume: - Issue: 6 Pages: 518-524

    • DOI

      10.1111/iju.14231

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of the Circadian Core Machinery in Mammals2020

    • Author(s)
      Umemura Yasuhiro, Yagita Kazuhiro
    • Journal Title

      Journal of Molecular Biology

      Volume: - Issue: 12 Pages: 3611-3617

    • DOI

      10.1016/j.jmb.2019.11.026

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output2019

    • Author(s)
      Ikeda Ryosuke、Tsuchiya Yoshiki、Koike Nobuya、Umemura Yasuhiro、Inokawa Hitoshi、Ono Ryutaro、Inoue Maho、Sasawaki Yuh、Grieten Tess、Okubo Naoki、Ikoma Kazuya、Fujiwara Hiroyoshi、Kubo Toshikazu、Yagita Kazuhiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10171-10171

    • DOI

      10.1038/s41598-019-46656-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human Circadian Molecular Oscillation Development Using Induced Pluripotent Stem Cells.2019

    • Author(s)
      Umemura Y, Maki I, Tsuchiya Y, Koike N, Yagita K
    • Journal Title

      J Biol Rhythms

      Volume: 34 Issue: 5 Pages: 525-532

    • DOI

      10.1177/0748730419865436

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids2021

    • Author(s)
      梅村康浩, 小池宣也, 土谷佳樹, 渡邊仁美, 近藤玄, 影山龍一郎, 八木田和弘
    • Organizer
      第28回日本時間生物学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 概日時計コア因子CLOCK/BMAL1による体節時計振動への干渉作用2021

    • Author(s)
      梅村康浩、小池宣也、土谷佳樹、渡邊仁美、近藤玄、影山龍一郎、八木田和弘
    • Organizer
      日本生理学会第113回近畿生理学談話会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いた概日時計の発生2019

    • Author(s)
      梅村康浩, 八木田和弘
    • Organizer
      第16回日本時間生物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒトiPS細胞を用いた概日時計の発生2019

    • Author(s)
      梅村康浩, 八木田和弘
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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