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The molecular mechanism by which cells respond to Fluid flow.

Research Project

Project/Area Number 18K14725
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionNational Center of Neurology and Psychiatry (2020)
Institute of Physical and Chemical Research (2018-2019)

Principal Investigator

Minegishi Katsura  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, リサーチフェロー (60568814)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords左右非対称 / 器官形成 / メカノセンサー / RNA結合タンパク質 / Nodal / Cerl2 / Dand5 / Pkd2 / 左右軸 / mRNAの分解 / 機械的刺激 / ノード / 左右非対称性 / node
Outline of Final Research Achievements

The left-right asymmetric morphogenesis of mammals is triggered by the leftward flow, which is generated by the rotating cilia on the node (E7.5). The mechanism by which flow stimuli is transmitted to the cell, was unknown.
Cerl2 is known as the earliest gene that has left-right asymmetric expression pattern. Cerl2 is expressed higher on the right side of node. This left-right asymmetric expression of Cerl2 is generated by the left side specific degradation of mRNA of Cerl2. The degradation of Cerl2 is induced by fluid flow stimuli via cation channel Pkd2. In this research, I found that the most proximal 200 nucleotide region of the 3'-UTR is essential for the asymmetric mRNA decay. I also demonstrated that RNA binding protein Bicc1 bind to the region, and CCR4-NOT is involved in the degradation mechanism of Cerl2. I expected that this study will lead the elucidation of the mechanism by which mechanical stimuli regulates gene expression.

Academic Significance and Societal Importance of the Research Achievements

細胞に加わる機械的刺激による遺伝子発現の制御は発生、加齢、メタボリズム、循環器の維持など多岐にわたる生命現象に関与している。本研究は機械刺激が遺伝子発現の左右差をもたらすメカニズムについての研究であるが、左右非対称な形態形成の理解にとどまらず、広く生物学に影響を与える一般的な原理、機構へと発展する可能性を秘めている。例えば、今回解析したPkd2は腎臓上皮細胞の繊毛に局在し水流のセンサーとしてはたらくことが報告されており、その機能欠損が嚢胞腎を引き起こすことも知られている。このことから、我々はノードと腎臓細胞において類似した機械的刺激を変換する機構が存在しているのではないかと考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Int'l Joint Research] EPFL(スイス)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] EPFL(スイス)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Nodal paralogues underlie distinct mechanisms for visceral left-right asymmetry in reptiles and mammals2020

    • Author(s)
      Kajikawa Eriko、Horo Uzuki、Ide Takahiro、Mizuno Katsutoshi、Minegishi Katsura、Hara Yuichiro、Ikawa Yayoi、Nishimura Hiromi、Uchikawa Masanori、Kiyonari Hiroshi、Kuraku Shigehiro、Hamada Hiroshi
    • Journal Title

      Nature Ecology & Evolution

      Volume: 4 Issue: 2 Pages: 261-269

    • DOI

      10.1038/s41559-019-1072-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components2020

    • Author(s)
      Teramoto Machiko、Sugawara Ryo、Minegishi Katsura、Uchikawa Masanori、Takemoto Tatsuya、Kuroiwa Atsushi、Ishii Yasuo、Kondoh Hisato
    • Journal Title

      Biology Open

      Volume: 9 Pages: 048728-048728

    • DOI

      10.1242/bio.048728

    • NAID

      120006859990

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ciliogenesis‐coupled accumulation of IFT‐B proteins in a novel cytoplasmic compartment2019

    • Author(s)
      Lamri Lynda、Twan Wang Kyaw、Katoh Takanobu A.、Botilde Yanick、Takaoka Katsuyoshi、Ikawa Yayoi、Nishimura Hiromi、Fukumoto Akemi、Minegishi Katsura、Mizuno Katsutoshi、Hamada Hiroshi
    • Journal Title

      Genes to Cells

      Volume: 24 Issue: 11 Pages: 731-745

    • DOI

      10.1111/gtc.12722

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 平面内細胞極性 (PCP) がもたらす左右軸の決定機構2019

    • Author(s)
      峰岸かつら, 濱田博司
    • Journal Title

      医学のあゆみ 細胞の極性化がもたらす生命現象

      Volume: 268(6) Pages: 474-480

    • Related Report
      2019 Research-status Report
  • [Presentation] Mechanism that fluid flow establishes left-right asymmetric decay of Cerl2 mRNA2018

    • Author(s)
      峰岸 かつら
    • Organizer
      Joint Annual Meeting of JSDB 51st and JSCB 70th
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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