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Mathematical modeling and computer simulation of brain development regulated by interplay of time and space

Planned Research

Project AreaInterplay of developmental clock and extracellular environment in brain formation
Project/Area Number 16H06486
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

Adachi Taiji  京都大学, ウイルス・再生医科学研究所, 教授 (40243323)

Co-Investigator(Kenkyū-buntansha) 亀尾 佳貴  京都大学, ウイルス・再生医科学研究所, 助教 (60611431)
武石 直樹  大阪大学, 基礎工学研究科, 助教 (30787669)
Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥134,290,000 (Direct Cost: ¥103,300,000、Indirect Cost: ¥30,990,000)
Fiscal Year 2020: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2019: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2018: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2017: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2016: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
Keywords脳・神経 / 発生・分化 / 細胞・組織 / 生物物理学 / 数理工学 / 生物物理
Outline of Final Research Achievements

To clarify the mechanism of brain development regulated by interplay of time and space, comprehensive understanding of the spatiotemporal mechanical behavior of brain tissues and the underlying multicellular dynamics is of great importance. Therefore, in this study, we have developed a mathematical model of brain morphogenesis that links tissue growth and deformation to cell proliferation and migration. The proposed mathematical model was validated through a reproduction of neuronal lamination in cerebral cortex. Then, this model was applied to the simulation of folia formation in cerebellar cortex to reveal the importance of fiber-guided neuronal migration. Furthermore, we proposed a novel approach to capture the overall view of mechanically admissible morphogenesis by describing the landscape of strain energy accumulated in the growing tissue.

Academic Significance and Societal Importance of the Research Achievements

本研究で構築した脳形態形成の数理モデルは、多細胞の複雑な相互作用と、それにより生じる組織の時空間的な挙動をコンピュータ内で同時に解析するためのフレームワークであり、形態形成を通じて脳の複雑な構造と機能が創発されるメカニズムを力学的・生化学的観点から理解するための新しい研究アプローチを提供するものである。また、滑脳症や多小脳回をはじめ、脳の構造に異常をきたす脳神経疾患の原因究明や治療法の確立など、将来の臨床医療への多大な貢献が期待される。

Report

(6 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (39 results)

All 2022 2021 2020 2019 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (36 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results)

  • [Journal Article] Cerebellar foliation via non-uniform cell accumulation caused by fiber-guided migration of granular cells2021

    • Author(s)
      Hironori Takeda, Yoshitaka Kameo, Takahiro Yamaguchi, Kazunori Nakajima, Taiji Adachi
    • Journal Title

      Journal of Biomechanical Science and Engineering

      Volume: 16 Issue: 1 Pages: 20-00516-20-00516

    • DOI

      10.1299/jbse.20-00516

    • NAID

      130008031763

    • ISSN
      1880-9863
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Continuum modeling for neuronal lamination during cerebral morphogenesis considering cell migration and tissue growth2020

    • Author(s)
      Hironori Takeda, Yoshitaka Kameo, Taiji Adachi
    • Journal Title

      Computer Methods in Biomechanics and Biomedical Engineering

      Volume: - Issue: 7 Pages: 799-805

    • DOI

      10.1080/10255842.2020.1852554

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An energy landscape approach to understanding variety and robustness in tissue morphogenesis2020

    • Author(s)
      Hironori Takeda, Yoshitaka Kameo, Yasuhiro Inoue and Taiji Adachi
    • Journal Title

      Biomechanics and Modeling in Mechanobiology

      Volume: 19 Issue: 2 Pages: 471-479

    • DOI

      10.1007/s10237-019-01222-5

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 神経線維の配向に依存した小脳の平行なしわ形成過程の力学的検討2022

    • Author(s)
      山口嵩洋,竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      日本機械学会第32回バイオフロンティア講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Mechanical modeling of brain morphogenesis caused by multicellular dynamics2022

    • Author(s)
      Yoshitaka Kameo, Hironori Takeda, Taiji Adachi
    • Organizer
      International Symposium on Development and Plasticity of Neural System
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞の増殖と移動にともなう脳形態形成の数理モデリング2021

    • Author(s)
      亀尾佳貴, 竹田宏典, 安達泰治
    • Organizer
      第60回日本生体医工学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生体組織の形態形成の理解に向けた連続体力学シミュレーション2021

    • Author(s)
      竹田宏典, 亀尾佳貴, 安達泰治
    • Organizer
      日本機械学会第33回バイオエンジニアリング講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 神経線維の配向による材料異方性を考慮した小脳しわ形成の有限要素解析2021

    • Author(s)
      山口嵩洋, 竹田宏典, 亀尾佳貴, 安達泰治
    • Organizer
      日本機械学会第33回バイオエンジニアリング講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生体組織の成長により生じる分岐現象のエネルギー地形に基づく理解2021

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      日本機械学会M&M2021材料力学カンファレンス
    • Related Report
      2020 Annual Research Report
  • [Presentation] Finite Element Analysis of Parallel Folding during Cerebellar Morphogenesis Considering Oriented Nerve Fibers2021

    • Author(s)
      Takahiro Yamaguchi, Hironori Takeda, Yoshitaka Kameo, Taiji Adachi
    • Organizer
      The 11th Asian-Pacific Conference on Biomechanics (APBiomech2021)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞移動と組織成長から生じる脳形態形成の有限要素解析2020

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      日本機械学会第31回バイオフロンティア講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Multiscale Biomechanics Approach to Understanding Roles of Forces in Multicellular Tissue Morphogenesis2019

    • Author(s)
      Adachi, T.
    • Organizer
      Tissue Engineering & Regenerative Medicine International Society - AP Chapter and the 7th Asian Biomaterials Congress (TERMIS-AP2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Biomechanics of Epithelial Morphogenesis: From Molecular Mechanofeedback to Tissue Deformation2019

    • Author(s)
      Adachi, T.
    • Organizer
      8th International Conference on Mechanics of Biomaterials and Tissues
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 組織形態形成における多様性と安定性の理解に向けた非線形連続体力学に基づくエネルギー地形アプローチの提案2019

    • Author(s)
      亀尾佳貴,竹田宏典,安達泰治
    • Organizer
      日本機械学会第32回計算力学講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エネルギー地形アプローチに基づく組織形態形成の多様性と安定性の探求(Exploring variety and robustness in tissue morphogenesis based on energy landscape approach)2019

    • Author(s)
      亀尾佳貴,竹田宏典,安達泰治
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳形態形成におけるニューロン移動と大脳成長の連成数理モデリング(A coupled mathematical modeling for neuronal migration and cerebral growth in brain morphogenesis)2019

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 上皮形態形成における力の役割:多階層バイオメカニクスアプローチ(Forces and their feedback in epithelial tissue morphogenesis: Multiscale biomechanics approach)2019

    • Author(s)
      安達泰治
    • Organizer
      第42回日本分子細胞生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 神経細胞移動にともなう脳形態形成の連続体力学モデル2019

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • 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] 生物の形態形成の力学:分子から組織まで2019

    • Author(s)
      安達泰治
    • Organizer
      理研シンポジウム:計算で物事を理解する予測する―データサイエンス, 自然知能, そして圏論へ―
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] In-silico and in-vitro Studies on Mechanofeedback in Multicellular Tissue Morphogenesis2018

    • Author(s)
      Taiji Adachi
    • Organizer
      International Conference on Medicine and Biology (ICMMB2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Force Feedback in Multicellular Morphogenesis from Molecule to Tissue: In vitro and in silico Studies2018

    • Author(s)
      Taiji Adachi
    • Organizer
      ASME 2018 NanoEngineering for Medicine and Biology Conference (NEMB)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多細胞組織の形態形成における分子・細胞バイオメカニクス:実験と数理アプローチ2018

    • Author(s)
      安達泰治
    • Organizer
      第18回日本蛋白質科学会年会, ワークショップ「発生ダイナミクス解明のためのツール開発とその応用」
    • Related Report
      2018 Annual Research Report
  • [Presentation] A Coupled Model of Cell Migration and Tissue Deformation for Simulating Cerebral Cortex Morphogenesis2018

    • Author(s)
      Yoshitaka Kameo, Hironori Takeda, Taiji Adachi
    • Organizer
      International Young Scientists Workshop on Neural Development & Stem Cells 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Finite Element Analysis of Coupled Behavior of Tissue Deformation and Cell Movement in Morphogenesis2018

    • Author(s)
      Hironori Takeda, Yoshitaka Kameo, Taiji Adachi
    • Organizer
      8th World Congress of Biomechanics (WCB2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] リーリンはN-cadherinを基盤とした神経細胞接着を2つの経路で誘導する2018

    • Author(s)
      林 周宏, 仲尾信彦, 井上聖香, 安達泰治, 久保健一郎, 仲嶋一範
    • Organizer
      第61回日本神経化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生体組織の成長と収縮のタイミングが形態形成に及ぼす影響2018

    • Author(s)
      竹田宏典, 亀尾佳貴, 安達泰治
    • Organizer
      日本機械学会第29回バイオフロンティア講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 形態形成における組織形態多様化の理解に向けた力学的アプローチ2018

    • Author(s)
      竹田宏典, 亀尾佳貴, 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
      2018 Annual Research Report
  • [Presentation] 細胞スケールの間質液流れに関する数値解析2018

    • Author(s)
      武石直樹, 重松大輝, 堀川健介, 和田成夫
    • 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
      2018 Annual Research Report
  • [Presentation] 組織形態形成における細胞移動と組織変形の連成モデリング2017

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳皮質形成における神経細胞運動の連続場モデリング2017

    • Author(s)
      Guyot Yann,安達泰治
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞接着を制限したメッシュ構造基板によるmES細胞の自己組織化誘導2017

    • Author(s)
      安藤悠太,オケヨケネディ,安達泰治
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 眼杯の形態形成を引き起こす細胞活動の力学的作用2017

    • Author(s)
      竹田宏典,亀尾佳貴,安達泰治
    • Organizer
      日本機械学会2017年度年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メッシュ構造基板を用いた接着領域制限下におけるmES細胞の未分化性評価2017

    • Author(s)
      安藤悠太,オケヨケネディ,安達泰治
    • Organizer
      日本機械学会2017年度年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞接着制限環境下におけるmES細胞の培養2017

    • Author(s)
      安藤悠太,オケヨケネディ,安達泰治
    • Organizer
      第40回日本バイオレオロジー学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Role of Mechanical Force Feedback in Multicellular Morphogenesis: in silico and in vitro Studies2016

    • Author(s)
      Taiji Adachi
    • Organizer
      The 16th International Conference on Biomedical Engineering (ICBME2016)
    • Place of Presentation
      National University of Singapore (Singapore)
    • Year and Date
      2016-12-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 立体組織の形態形成における力の役割:in silico実験2016

    • Author(s)
      安達泰治
    • Organizer
      日本バイオマテリアル学会シンポジウム2016
    • Place of Presentation
      福岡国際会議場(福岡県福岡市・博多区)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Finite Element Analysis of Optic-cup Morphogenesis Mechanically Regulated by Tissue Growth and Constriction2016

    • Author(s)
      Hironori Takeda, Yoshitaka Kameo, Taiji Adachi
    • Organizer
      日本機械学会第27回バイオフロンティア講演会
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell Shapes within Self-organized Optic Cup from Embryoid Body2016

    • Author(s)
      Yuta Ando, Junko Sunaga, Taiji Adachi
    • Organizer
      日本機械学会第27回バイオフロンティア講演会
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Computational Biomechanics of Multicellular Tissue Morphogenesis2016

    • Author(s)
      Taiji Adachi
    • Organizer
      The 3rd Joint Workshop between E-JUST and SRTA-City on Advanced Materials and Its Applications
    • Place of Presentation
      Egypt-Japan University of Science and Technology (Egypt)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-07-04   Modified: 2023-01-30  

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