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Molecular mechanisms underlying the generation and transduction of mechanical forces during brain development

Planned Research

Project AreaInterplay of developmental clock and extracellular environment in brain formation
Project/Area Number 16H06484
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

Kengaku Mineko  京都大学, 高等研究院, 教授 (10303801)

Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥148,850,000 (Direct Cost: ¥114,500,000、Indirect Cost: ¥34,350,000)
Fiscal Year 2020: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
Fiscal Year 2019: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
Fiscal Year 2018: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
Fiscal Year 2017: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
Fiscal Year 2016: ¥31,850,000 (Direct Cost: ¥24,500,000、Indirect Cost: ¥7,350,000)
Keywords発生・分化 / 細胞・組織 / 脳・神経
Outline of Final Research Achievements

We analyzed the impact of the mechanical properties of the developing brain tissue and cells in the control of the fate, position and shape of neurons in the well-organized cortex. We found that neurons switch the actomyosin force generation mechanisms in response to the mechanical stress of the surrounding microenvironment. We also found that the nuclei of newborn neurons are extremely soft due to its special nuclear lamina structure. The soft nucleus squeeze into the narrow tissue spaces against the shear stress by sharp deformation and rotation driven by the dynamic force of microtubule motors. We also proved that dendritic filopodia act as mechanosensors for space exploration and control the spatial distribution of dendritic arbors where collisions between projections do not occur. Furthermore, we developed a gel substrate that reproduces the softness of brain tissue and established a protocol to promote neuronal differentiation from neural stem cells.

Academic Significance and Societal Importance of the Research Achievements

これまでの脳発生研究は、化学シグナルの連鎖によるプログラムの進行と捉えられてきた。本研究は、ニューロンや脳組織の物理的な性質による空間的束縛の影響下で、脳皮質発生を担うニューロン細胞運動が効果的に駆動される力学的制御機構の一端を明らかにした点で、脳皮質構築の形成機構の理解にブレークスルーをもたらしたと考える。また、ニューロンの力学的性質を計測する微小力学計測技術を確立し、緻密な細胞配向と突起空間分布の再現が不可欠な脳組織のin vitro3D再構築の基盤技術に発展した。今後器質的に損傷した脳の再生医療分野に貢献できる可能性がある。

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

    (47 results)

All 2021 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (9 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (23 results) (of which Int'l Joint Research: 11 results,  Invited: 17 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] Mechanobiology Institute(シンガポール)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Korean Brain Research Institute(韓国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Heidelberg University(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Mechanobiology Institute(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Korean Brain Research Institute(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Heidelberg University(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Mechanobiology Institute(シンガポール)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Korean Brain Research Institute(韓国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Heidelberg University(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking2021

    • Author(s)
      Nakato Mitsuhiro、Shiranaga Naoko、Tomioka Maiko、Watanabe Hitomi、Kurisu Junko、Kengaku Mineko、Komura Naoko、Ando Hiromune、Kimura Yasuhisa、Kioka Noriyuki、Ueda Kazumitsu
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100166-100166

    • DOI

      10.1074/jbc.ra120.015997

    • NAID

      120007177776

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] βIII spectrin controls the planarity of Purkinje cell dendrites by modulating perpendicular axon-dendrite interactions2020

    • Author(s)
      Fujishima Kazuto、Kurisu Junko、Yamada Midori、Kengaku Mineko
    • Journal Title

      Development

      Volume: 147 Issue: 24

    • DOI

      10.1242/dev.194530

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanical regulation of nuclear translocation in migratory neurons2020

    • Author(s)
      N. Nakazawa and M. Kengaku
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 150-150

    • DOI

      10.3389/fcell.2020.00150

    • NAID

      120006813309

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes2020

    • Author(s)
      Ochi Y, Ogawa Seishi., et al.
    • Journal Title

      Cancer Discov

      Volume: - Issue: 6 Pages: 836-853

    • DOI

      10.1158/2159-8290.cd-19-0982

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dendritic Self-Avoidance and Morphological Development of Cerebellar Purkinje Cells2019

    • Author(s)
      Kazuto Fujishima, Kelly Kawabata Galbraith and Mineko Kengaku
    • Journal Title

      The Cerebellum

      Volume: 17 Issue: 6 Pages: 701-708

    • DOI

      10.1007/s12311-018-0984-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple roles of the actin and microtubule-regulating formins in the developing brain2019

    • Author(s)
      Kawabata Galbraith Kelly、Kengaku Mineko
    • Journal Title

      Neuroscience Research

      Volume: 138 Pages: 59-69

    • DOI

      10.1016/j.neures.2018.09.008

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] Cytoskeletal control of nuclear migration in neurons and non-neuronal cells2018

    • Author(s)
      KENGAKU Mineko
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 94 Issue: 9 Pages: 337-349

    • DOI

      10.2183/pjab.94.022

    • NAID

      130007503358

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2018-11-09
    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] MTSS1 Regulation of Actin-Nucleating Formin DAAM1 in Dendritic Filopodia Determines Final Dendritic Configuration of Purkinje Cells2018

    • Author(s)
      Kawabata Galbraith Kelly、Fujishima Kazuto、Mizuno Hiroaki、Lee Sung-Jin、Uemura Takeshi、Sakimura Kenji、Mishina Masayoshi、Watanabe Naoki、Kengaku Mineko
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 1 Pages: 95-106

    • DOI

      10.1016/j.celrep.2018.06.013

    • NAID

      120006489939

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Local traction force in the proximal leading process triggers nuclear translocation during neuronal migration2018

    • Author(s)
      Umeshima Hiroki、Nomura Ken-ichi、Yoshikawa Shuhei、Horning Marcel、Tanaka Motomu、Sakuma Shinya、Arai Fumihito、Kaneko Makoto、Kengaku Mineko
    • Journal Title

      Neurosci Res.

      Volume: in press Pages: 38-48

    • DOI

      10.1016/j.neures.2018.04.001

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nesprins and opposing microtubule motors generate a point force that drives directional nuclear motion in migrating neurons2018

    • Author(s)
      Wu You Kure、Umeshima Hiroki、Kurisu Junko、Kengaku Mineko
    • Journal Title

      Development

      Volume: 145 Issue: 5

    • DOI

      10.1242/dev.158782

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surface chemistry for cytosolic gene delivery and photothermal transgene expression by gold nanorods2017

    • Author(s)
      Nakatsuji Hirotaka、Kawabata Galbraith Kelly、Kurisu Junko、Imahori Hiroshi、Murakami Tatsuya、Kengaku Mineko
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-04912-1

    • NAID

      120006323754

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thyroid hormone induces PGC-1α during dendritic outgrowth in mouse cerebellar Purkinje cells2017

    • Author(s)
      Hatsukano T., Kurisu J., Fukumitsu K., Fujishima K., and Kengaku M.
    • Journal Title

      Front. Cell. Neurosci.

      Volume: 印刷中 Pages: 1-14

    • DOI

      10.3389/fncel.2017.00133

    • NAID

      120006318874

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Neuronal migration in 3D brain tissue.2020

    • Author(s)
      見学美根子
    • Organizer
      第14回ニッチ脳神経脈管カンファレンス
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Mechanical stress by extracellular confinement trigger a mode transition of neuronal migration.2020

    • Author(s)
      Naotaka Nakazawa, Gianluca Grenci, Mineko Kengaku
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Beta IIIスペクトリンのプルキンエ細胞-平行線維間の直交回路形成における役割.2020

    • Author(s)
      藤島和人、見学美根子
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The dynamic interplay between microtubule-based motors and nuclear movement in migrating cerebellar granule cells.2020

    • Author(s)
      Chuying Zhou, You Kure Wu, Mineko Kengaku
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cytoskeletal regulation of Purkinje cell dendritic arbor morphology. プルキンエ細胞樹状突起形態形成の細胞骨格制御メカニズム2020

    • Author(s)
      Kazuto Fujishima, Mineko Kengaku
    • Organizer
      第53回日本発生生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Nuclear Migration in 3D Brain Tissue Driven by Cytoskeletal Forces.2019

    • Author(s)
      You Kure Wu, Chuying Zhou, Hiroki Umeshima, Naotaka Nakazawa, Mineko Kengaku
    • Organizer
      20th LSACJ2019-International Conference on Interdisciplinary Life Sciences 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cytoskeletal forces driving nuclear migration in developing neurons.2019

    • Author(s)
      Mineko Kengaku, You Kure Wu, Naotaka Nakazawa, Gianluca Grenci
    • Organizer
      The 10th IBRO World Congress of Neuroscience IBRO2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell-extrinsic control of dendritic tree patterns of the cerebellar Purkinje cell.2019

    • Author(s)
      Kazuto Fujishima, Kelly Kawabata-Galbraith, Mineko Kengaku
    • Organizer
      Current Trends and Future Directions of Synapse-Circuit Plasticity Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 発生中のニューロン核移動を制御する細胞骨格モーターの力発生機構.2019

    • Author(s)
      呉攸、Chuying Zhou、梅嶋宏樹、Gianluca Grenci、中澤直高、見学美根子
    • Organizer
      第52回日本発生生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳発生におけるニューロン突起パターンと回路のジオメトリーを決定する分子細胞機構.2019

    • Author(s)
      藤島和人、山田緑、栗栖純子、見学美根子
    • Organizer
      第52回日本発生生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] High resolution imaging of cytoskeletal dynamics in developing neurons.2019

    • Author(s)
      Mineko Kengaku
    • Organizer
      Carl Zeiss Microscopy Seminar
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cytoskeletal control of neuronal migration in the developing brain.2019

    • Author(s)
      Mineko Kengaku
    • Organizer
      The SPIRITS International Symposium-2019 Regulation of cell fate and disease treatment
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] High-resolution Imaging of Neuronal Migration in the Developing Brain.2018

    • Author(s)
      Mineko Kengaku
    • Organizer
      Kyoto University-UCLA International Symposium/25th iCeMS International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cytoskeletal control of nuclear movement during neuronal migration.2018

    • Author(s)
      Mineko Kengaku
    • Organizer
      Capital Medical University Symposium ‘A New Era of Molecular and Cellular Neuroscience’
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 培養再構成系を用いた脳発生研究. Studying cell dynamics in the developing brain using in vitro reconstruction systems.2018

    • Author(s)
      見学美根子
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dynamics and mechanisms of nuclear migration in brain cells.2018

    • Author(s)
      Mineko Kengaku
    • Organizer
      iCeMS-iTHEMS Joint Workshop on Interdisciplinary Biology
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of cytoarchitecture formation of cerebellar neurons.2018

    • Author(s)
      Kazuto Fujishima and Mineko Kengaku
    • Organizer
      The 3rd Japan-US Technical Information Exchange Forum Blast Injury
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 小脳皮質形成を司る細胞骨格分子のダイナミクスとその制御2017

    • Author(s)
      見学美根子
    • Organizer
      立命館大学システム視覚科学研究センターセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Developing neurons on the move - dynamic sculpting of one-of-a-kind dendritic trees.2017

    • Author(s)
      Mineko Kengaku
    • Organizer
      BSI Retreat 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Molecular basis of the mechanical force driving neuronal migration in the developing brain.2017

    • Author(s)
      Mineko Kengaku, You Kure Wu and Hiroki Umeshima
    • Organizer
      Joint Meeting of the German and Japanese Societies of Developmental Biologists
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 移動ニューロンの核ダイナミクスを制御する細胞骨格. Cytoskeletal control of dynamic motility of the nucleus during neuronal migration.2016

    • Author(s)
      見学美根子、呉攸、梅嶋宏樹
    • Organizer
      第39回日本神経科学大会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] The molecular nature of the force driving nuclear transport during neuronal migration.2016

    • Author(s)
      Mineko Kengaku
    • Organizer
      Swiss-Kyoto Joint Symposium on Life Science
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics underlying cell architecture formation in the developing brain.2016

    • Author(s)
      Mineko Kengaku
    • Organizer
      Center for Functional Connectomics Seminar, Korea Institute of Science and Technology
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 京大発! フロンティア生命科学2018

    • Author(s)
      京都大学大学院生命科学研究科
    • Total Pages
      336
    • Publisher
      講談社サイエンティフィク
    • ISBN
      9784065038017
    • Related Report
      2017 Annual Research Report
  • [Book] 脳神経化学2018

    • Author(s)
      森 泰生、尾藤 晴彦
    • Total Pages
      368
    • Publisher
      化学同人
    • ISBN
      9784759817263
    • Related Report
      2017 Annual Research Report
  • [Remarks] 脳構築における発生時計と場の連携

    • URL

      http://www.time.icems.kyoto-u.ac.jp/

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report

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

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