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Mathematical and Mechanical principles of the formation of three-dimensional shapes in multicellular tissues

Planned Research

Project AreaDiscovery of the logic that establishes the 3D structure of organisms
Project/Area Number 15H05861
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

Inoue Yasuhiro  京都大学, 工学研究科, 教授 (80442929)

Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥71,110,000 (Direct Cost: ¥54,700,000、Indirect Cost: ¥16,410,000)
Fiscal Year 2019: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2018: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2017: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2016: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2015: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Keywords形態形成 / 上皮組織 / 多細胞力学 / 数理モデル / シミュレーション / 計算力学 / 成虫原基 / 折り畳み / 生物物理学 / 多細胞動力学 / 生物物理 / 計算物理
Outline of Final Research Achievements

In tissue morphogenesis, individual cells generate forces that exert on other cells. Tissue deformations are driven by those forces. In this study, to understand the dynamics of epithelial morphogenesis, we developed a mathematical model (3D vertex model) that captures cell mechanical behaviors and applied it to the analysis of the morphogenesis. We reveal that there is a mechanical role to proceed morphogenesis robustly in response to mechanical perturbations, a mechanism by which 3D formation of epithelial tissue arises from spatial pattern of gene expression at multicellular level, and a mechanism by which epithelial tissue folds spontaneously. Through these studies, we proposed the importance of understanding mechanics at the cellular level, and greatly developed mechanics on morphogenesis as an academic discipline.

Academic Significance and Societal Importance of the Research Achievements

生物の形ができる原理の解明は基礎生物学の最重要課題の一つである。この課題では、3Dの形態形成を扱うため、形の変化を記述する力学の観点から発生現象を捉える必要があったが、その理論的手法は確立していなかった。本研究では、細胞個々の力学を3Dで捉える手法として、3Dバーテックスモデルを確立し、実際の発生現象の解析に応用することで、これまで、遺伝子発現レベルの場の区分け(2D情報)からは読み取れなかった形態形成の力学的な因果関係を明らかにした。これまで、物理学や機械工学の範疇と考えられていた力学を、基礎生物学の領域に展開したことにより、形態形成の仕組みに関して、新たな理解が得られるようになった。

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (2 results) Remarks (5 results)

  • [Int'l Joint Research] Purdue University/Louisiana State University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Purdue University/Louisiana State University(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Collective and contractile filament motions in the myosin motility assay2020

    • Author(s)
      Jung Wonyeong、Fillenwarth Luke A.、Matsuda Atsushi、Li Jing、Inoue Yasuhiro、Kim Taeyoon
    • Journal Title

      Soft Matter

      Volume: 16 Issue: 6 Pages: 1548-1559

    • DOI

      10.1039/c9sm02082a

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Epithelial tissue folding pattern in confined geometry2019

    • Author(s)
      Inoue Yasuhiro、Tateo Itsuki、Adachi Taiji
    • Journal Title

      Biomechanics and Modeling in Mechanobiology

      Volume: 19 Issue: 3 Pages: 815-822

    • DOI

      10.1007/s10237-019-01249-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mobility of Molecular Motors Regulates Contractile Behaviors of Actin Networks2019

    • Author(s)
      Matsuda Atsushi、Li Jing、Brumm Peter、Adachi Taiji、Inoue Yasuhiro、Kim Taeyoon
    • Journal Title

      Biophysical Journal

      Volume: 116 Issue: 11 Pages: 2161-2171

    • DOI

      10.1016/j.bpj.2019.04.018

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PCP-dependent transcellular regulation of actomyosin oscillation facilitates convergent extension of vertebrate tissue2019

    • Author(s)
      Shindo Asako、Inoue Yasuhiro、Kinoshita Makoto、Wallingford John B.
    • Journal Title

      Developmental Biology

      Volume: 446 Issue: 2 Pages: 159-167

    • DOI

      10.1016/j.ydbio.2018.12.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanical role of the spatial patterns of contractile cells in invagination of growing epithelial tissue2017

    • Author(s)
      Inoue Yasuhiro、Watanabe Tadashi、Okuda Satoru、Adachi Taiji
    • Journal Title

      Development, Growth & Differentiation

      Volume: 59 Issue: 5 Pages: 444-454

    • DOI

      10.1111/dgd.12374

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanical roles of apical constriction, cell elongation, and cell migration during neural tube formation in Xenopus, Biomechanics and Modeling in Mechanobiology2016

    • Author(s)
      Yasuhiro Inoue, Makoto Suzuki, Tadashi Watanabe, Naoko Yasue, Itsuki Tateo, Taiji Adachi, Naoto Ueno
    • Journal Title

      Biomechanics and Modeling in Mechanobiology

      Volume: 15 Issue: 6 Pages: 1733-1746

    • DOI

      10.1007/s10237-016-0794-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Mathematical modeling of epithelial folding with cell proliferation depending on the curvature of the tissue2019

    • Author(s)
      Kentaro Morikawa, Yasuhiro Inoue
    • Organizer
      5th Computational Chemistry Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織スケールのミオシン収縮ケーブルによる上皮陥入シミュレーション2019

    • Author(s)
      渡辺章太郎, 井上康博
    • Organizer
      日本機械学会第32回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 発生過程の組織変形における細胞集団運動の数理モデル2019

    • Author(s)
      齋梧 等, 井上 康博, 安達 泰治
    • Organizer
      日本機械学会第31回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Folding pattern formation in a confined epithelial cell sheet2018

    • Author(s)
      Yasuhiro Inoue
    • Organizer
      第56回日本生物物理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanochemical interplays in multicellular dynamics during tissue morphogenesis2018

    • Author(s)
      Yasuhiro Inoue
    • Organizer
      The Second Workshop on Microscopic Simulation and Cell Experiments for Biological Systems
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 上皮折りたたみの多細胞力学シミュレーション2017

    • Author(s)
      井上康博, 立尾樹, 安達泰治
    • Organizer
      日本機械学会・第29回バイオエンジニアリング講演会
    • Place of Presentation
      名古屋
    • Year and Date
      2017-01-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Multiscale interplay between intracellular and multicellular dynamics in tissue morphogenesis2017

    • Author(s)
      Yasuhiro Inoue
    • Organizer
      2017 Cellular and Molecular Bioengineering Conference
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2017-01-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Three-dimensional vertex simulation of multicellular dynamics for understanding mechanics of epithelial tissue morphogenesis2016

    • Author(s)
      Yasuhiro Inoue
    • Organizer
      Bioimage Informatics Conference 2016
    • Place of Presentation
      Singapore
    • Year and Date
      2016-10-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 3Dバーテックスモデルによる上皮折り畳みシミュレーション2015

    • Author(s)
      井上康博,安達泰治
    • Organizer
      RIMS研究集会 第12回生物数学の理論とその応用-遷移過程に現れるパターンの解明に向けて
    • Place of Presentation
      京都大学数理解析研究所
    • Year and Date
      2015-11-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Spatially Patterns of Constricting Cells Determine te Direction of Out-of-plane Deformation of Epithelial Sheet2015

    • Author(s)
      Yasuhiro Inoue, Tadashi Watanabe, Taiji Adachi
    • Organizer
      iCeMS International Symposium: Hierarchical Dynamics in Soft Materials and Biological Matter
    • Place of Presentation
      京都大学
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 実験医学増刊 生命科学で使える はじめての数理モデルとシミュレーション (担当:第4章・11)2017

    • Author(s)
      井上 康博
    • Total Pages
      239
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Book] メカノバイオロジー:細胞が力を感じ応答する仕組み(曽我部正博編)2015

    • Author(s)
      井上康博, 安達泰治(分担執筆)
    • Total Pages
      332
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Remarks]

    • URL

      https://kyouindb.iimc.kyoto-u.ac.jp/j/lS2qY

    • Related Report
      2019 Annual Research Report
  • [Remarks]

    • URL

      https://researchmap.jp/yasuhiroinoue

    • Related Report
      2019 Annual Research Report
  • [Remarks] 京都大学教育研究活動データベース

    • URL

      https://kyouindb.iimc.kyoto-u.ac.jp/j/lS2qY

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://www.frontier.kyoto-u.ac.jp/bf05/membersHP/inoue/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学 教育活動データベース

    • URL

      https://kyouindb.iimc.kyoto-u.ac.jp/j/lS2qY

    • Related Report
      2015 Annual Research Report

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Published: 2015-07-02   Modified: 2022-11-04  

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