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Molecular and dynamic basis of axon guidance by mechanical stimulation

Research Project

Project/Area Number 17K19453
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Neuroscience and related fields
Research InstitutionKyoto University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 亀井 謙一郎  京都大学, 高等研究院, 准教授 (00588262)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords軸索ガイダンス / ナノパターン / メカノバイオロジー / 細胞密着 / 細胞接着
Outline of Final Research Achievements

We sought to identify a novel mechanism of axon guidance by mechanical properties of the developing brain tissue. Using nanoimprint lithography, we developed culture substrates with various line & space patterns and observed the growth of primary hippocampal and cerebellar neurons. We found that hippocampal neurons extend the axon perpendicularly to the narrow lines below 200 nm, while it runs along the thicker lines, indicating that axonal growth is influenced by the shape of extracellular substrates. Traction force microscopy revealed the generation of centripetal force at the periphery of extending growth cones. In contrast, actin fibers form random meshwork in the growth cones independently of the growth orientation as observed by scanning electron microscopy. Ongoing efforts to improve the patterned substrates with novel smart materials will clarify dynamic force generation during the oriented axonal elongation by confocal and TIRF microscopy.

Academic Significance and Societal Importance of the Research Achievements

神経回路配線は遺伝的プログラムに従ったタンパク質情報で規定されるというパラダイムを超え、組織空間の機械的性質が軸索走行の制御に関わることが示唆された。また最新の生物工学、材料科学の技術を取り入れ、細胞の微小物理量を計測する新たな解析系の開発を行なった。これらの知見と技術を発展させれば、細胞自身のもつ力学的性質を利用して細胞運動を自在に誘導するスキャフォールドをデザインすることが可能となり、将来、器質的・機能的に損傷した脳部位への再生医療の基盤技術となることが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Book (2 results)

  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] レスター大学(英国)

    • Related Report
      2017 Research-status Report
  • [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] Dynamic Contact Guidance of Myoblasts by Feature Size and Reversible Switching of Substrate Topography: Orchestration of Cell Shape, Orientation, and Nematic Ordering of Actin Cytoskeletons.2018

    • Author(s)
      Linke, P.; Suzuki, R.; Yamamoto, A.; Nakahata, M.; Kengaku, M.; Fujiwara, T.; Ohzono, T.* & Tanaka, M.*
    • Journal Title

      Langmuir

      Volume: special issue Issue: 23 Pages: 7538-7551

    • DOI

      10.1021/acs.langmuir.8b02972

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic Interaction Between Microtubules and the Nucleus Regulates Nuclear Movement During Neuronal Migration2018

    • Author(s)
      Wu You Kure、Kengaku Mineko
    • Journal Title

      Journal of Experimental Neuroscience

      Volume: 12 Pages: 117906951878915-117906951878915

    • DOI

      10.1177/1179069518789151

    • Related Report
      2018 Annual Research Report
    • 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
      2017 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [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/25th iCeMS International Symposium “Harnessing Physical Forces for Medical Application: Convergence of Physics, Nanomaterials, Cell Biology and Cancer Research”
    • 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)
      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2018

    • Author(s)
      見学美根子
    • Organizer
      立命館大学セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Developing neurons on the move-dynamic sculpting of one-of-a-kind dendritic trees2017

    • Author(s)
      Mineko Kengaku
    • Organizer
      BSI Retreat 2017
    • Related Report
      2017 Research-status Report
    • 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
      325
    • Publisher
      講談社
    • ISBN
      9784065038017
    • Related Report
      2017 Research-status 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 Research-status Report

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Published: 2017-07-21   Modified: 2022-02-22  

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