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To elucidate the mechanisms of mechano-transduction for the cardiac lumen morphogenesis

Research Project

Project/Area Number 21K06764
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionThe University of Tokushima (2023)
National Cardiovascular Center Research Institute (2021-2022)

Principal Investigator

FUKUI Hajime  徳島大学, 先端酵素学研究所, 准教授 (80551506)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords心臓管腔形成 / ゼブラフィッシュ / 力学応答 / 血流 / メカノトランスダクション / 心臓弁形成 / 血行力学特性
Outline of Research at the Start

心臓弁形成は、遺伝学的な制御をうけるシグナル調節機構と、物理学的に調節される力学応答機構が協調的に働くことで進行する。遺伝的に制御されたシグナル因子が弁形成に関わることが研究されてきた一方、力学応答機構の詳細は不明であった。本申請者は拍動する状態の生体心臓を解析し、力学情報が「弁形成時期に限って、弁領域特異的に」化学シグナルに変換される機構を明らかにした。しかし、恒常的な力学刺激(拍動・血流)がどのようにして適切に弁領域で調節されるのか、その機構は未だに不明である。本研究では心臓弁形成を制御する力学応答性の化学シグナルがどこから・どのように入力されるのかを明確にする。

Outline of Final Research Achievements

Cardiac lumen is constituted by endocardial cells. Endocardial cells are constantly sensed physical stress, such as pulsation and blood flow. In this project, we applied zebrafish embryos and performed both biological and biophysical approaches to accurately define the mechanical response in the heart.
We first found that (1) forces-dependent signal is triggered from the cardiac luminal side in endocardial cells. Next, (2) we developed a magnetic manipulation method into the cardiac lumen and then found that the properties of tangential stress (e.g. shear stress), not vertical stress, are a main regulator for the mechanical signal in endocardial cells. We also discovered that (3) intracellular signals are activated in endocardial cells in response to bidirectional blood flow. Further investigation will allow us to define the force effects that occur within the cardiac lumen.

Academic Significance and Societal Importance of the Research Achievements

心臓での力学応答の重要性は明らかであるものの、生体の中で実際におこる直接的な力学応答機構と、形態形成における明確な力学作用機序についてはほとんど示されていない。本研究は、独自に開発した生物学応答と物理学情報を直接的に関連付ける分野融合アプローチ:「生体心臓に対して人為的に力を操作することで出力される化学シグナル変動の定量的解析」によって、これまで理解することができなかった機構を明らかにする意義をもつ。本成果より、弁形成における「流れ」と「拍動」の力学情報の違いを明確に区別する研究への展開が期待できる。また、他の恒常的刺激を感受する臓器、骨格や筋肉についての研究への波及効果が期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (34 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (8 results) Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 8 results) Book (5 results) Remarks (2 results)

  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Peking University(中国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] IGBMC/Institut Jacques Monod(フランス)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Calcium signal analysis in the zebrafish heart via phase matching of the cardiac cycle2024

    • Author(s)
      Zhang RJ, Vermot J, Gherardi R, Fukui H, Chow RW
    • Journal Title

      bio-protocol

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish2023

    • Author(s)
      Hiroyuki Nakajima, Hiroyuki Ishikawa, Takuya Yamamoto, Ayano Chiba, Hajime Fukui, Keisuke Sako, Moe Fukumoto, Kenny Mattonet, Hyouk-Bum Kwon, Subhra P Hui, Gergana D Dobreva, Kazu Kikuchi, Christian S M Helker, Didier Y R Stainier, Naoki Mochizuki
    • Journal Title

      Developmental Cell

      Volume: 58 Issue: 3 Pages: 224-238

    • DOI

      10.1016/j.devcel.2022.12.013

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular mechanical forces drive endocardial cell volume decrease during zebrafish cardiac valve morphogenesis2022

    • Author(s)
      Vignes Helene、Vagena-Pantoula Christina、Prakash Mangal、Fukui Hajime、Norden Caren、Mochizuki Naoki、Jug Florian、Vermot Julien
    • Journal Title

      Developmental Cell

      Volume: 57 Issue: 5 Pages: 598-609.e5

    • DOI

      10.1016/j.devcel.2022.02.011

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling2022

    • Author(s)
      Chow Renee Wei-Yan、Fukui Hajime、Chan Wei Xuan、Tan Kok Soon Justin、Roth St?phane、Duchemin Anne-Laure、Messaddeq Nadia、Nakajima Hiroyuki、Liu Fei、Faggianelli-Conrozier Nathalie、Klymchenko Andrey S.、Choon Hwai Yap、Mochizuki Naoki、Vermot Julien
    • Journal Title

      PLOS Biology

      Volume: 20 Issue: 1 Pages: e3001505-e3001505

    • DOI

      10.1371/journal.pbio.3001505

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bioelectric signaling and the control of cardiac cell identity in response to mechanical forces.2021

    • Author(s)
      Fukui H, Chow RW, Xie J, Foo YY, Yap CH, Minc N, Mochizuki N, Vermot J
    • Journal Title

      Science

      Volume: 374 Issue: 6565 Pages: 351-354

    • DOI

      10.1126/science.abc6229

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 外力に応答する化学的シグナル可視化から観る心臓管腔形成機構2024

    • Author(s)
      福井 一
    • Organizer
      徳島大学 医光融合研究シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心臓管腔形成を制御する血流の力学特性を認識した力学応答機構2024

    • Author(s)
      福井 一
    • Organizer
      第129回日本解剖学会総会・全国学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 血流が規定する心臓管腔形成機構2023

    • Author(s)
      福井 一
    • Organizer
      第8回血管生物若手研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Bidirectional flow forces instruct endocardial cell identity for the cardiac lumen morphogenesis2023

    • Author(s)
      Hajime Fukui, Naoki Mochizuki
    • Organizer
      第75回日本細胞生物学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 組織形成の理解に向けた力の操作と力学生体シグナル研究2023

    • Author(s)
      福井 一
    • Organizer
      先端酵素学研究所シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心臓弁形成を制御する「血流ベクトル」を認識した力学応答原理の解明2023

    • Author(s)
      福井 一
    • Organizer
      山内進循環器病研究助成 第4回研究発表会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心臓形成の理解にむけた生体力学シグナル研究2023

    • Author(s)
      福井 一
    • Organizer
      第22回日本心臓血管発生研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Bidirectional flow forces instruct endocardial cell identity for the cardiac valve morphogenesis2023

    • Author(s)
      Hajime FUKUI
    • Organizer
      BDR symposium 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bidirectional flow forces instruct endocardial cell identity for the cardiac valve formation2022

    • Author(s)
      Hajime FUKUI, Julien VERMOT and Naoki Mochizuki
    • Organizer
      3rd Franco-Japanese Developmental biology meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心臓弁形成を調節する新たな力学応答シグナルの解明2022

    • Author(s)
      福井 一
    • Organizer
      CVMW2022 日本血管生物医学会 第7回血管生物若手研究会優秀賞・最優秀賞講演
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Bidirectional flow forces instruct endocardial cell identity for the cardiac valve development2022

    • Author(s)
      福井 一
    • Organizer
      CVMW2022 BCVRシンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 「力」による心臓弁の造形2022

    • Author(s)
      福井 一
    • Organizer
      第7回 日本血管生物医学会 血管生物若手研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 力学刺激に依存した化学シグナル応答による心臓弁形成機構2021

    • Author(s)
      福井 一, 望月 直樹, Julien VERMOT
    • Organizer
      第94回 日本生化学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Molecular control of endocardial cell fate in response to mechanical forces during cardiac valve formation2021

    • Author(s)
      Hajime FUKUI
    • Organizer
      第5回 BCVR
    • Related Report
      2021 Research-status Report
  • [Book] 実験医学4月号 「力」に応答した生体電気シグナルによる心臓弁形成メカニズム2022

    • Author(s)
      福井 一
    • Total Pages
      4
    • Publisher
      羊土社
    • ISBN
      9784758125543
    • Related Report
      2022 Research-status Report
  • [Book] 臨床免疫・アレルギー科9月号 機械的な力に応じた生体電気シグナル伝達は心臓弁となる細胞運命を制御する2022

    • Author(s)
      福井 一
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2022 Research-status Report
  • [Book] 医学のあゆみ12月号 メカノトランスダクションによる心臓血管発生制御2022

    • Author(s)
      福井 一、中嶋 洋行、望月 直樹
    • Total Pages
      5
    • Publisher
      医歯薬出版
    • Related Report
      2022 Research-status Report
  • [Book] 実験医学2022年4月号2022

    • Author(s)
      福井 一
    • Total Pages
      129
    • Publisher
      羊土社
    • ISBN
      9784758125543
    • Related Report
      2021 Research-status Report
  • [Book] 循環器疾患(2021 下巻)モデル動物の作製と利用2021

    • Author(s)
      福井 一, 迫 圭輔, 望月 直樹
    • Total Pages
      414
    • Publisher
      LIC
    • ISBN
      9784900487598
    • Related Report
      2021 Research-status Report
  • [Remarks] 研究室(生体力学シグナル分野)紹介ページ

    • URL

      https://www.iams.tokushima-u.ac.jp/lab/fukui/

    • Related Report
      2023 Annual Research Report
  • [Remarks]

    • URL

      https://www.imperial.ac.uk/news/231714/bioengineers-find-heart-valves-grow-wrong/

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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