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新規素材とマイクロ加工技術で再現する脳微小空間を用いたニューロン遊走機構の解析

Research Project

Project/Area Number 18KK0212
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionKyoto University

Principal Investigator

見学 美根子  京都大学, 高等研究院, 教授 (10303801)

Co-Investigator(Kenkyū-buntansha) 宇都 甲一郎  国立研究開発法人物質・材料研究機構, 機能性材料研究拠点, 独立研究者 (30597034)
中澤 直高  京都大学, 高等研究院, 特定助教 (90800780)
Project Period (FY) 2018-10-09 – 2023-03-31
Project Status Granted (Fiscal Year 2021)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsメカノバイオロジー / マイクロファブリケーション / ニューロン移動 / 神経発生 / 細胞骨格 / ライブイメージング
Outline of Annual Research Achievements

国際共同研究ではマイクロリソグラフィー技術を用いて作成した通路状のマイクロスペーサー基板および市販の多孔性フィルター膜を用いて、顆粒細胞が神経組織間隙を隘路遊走する運動制御機構を解析した。薬理実験と分子操作実験で、隘路侵入により細胞膜張力が上昇し、機械刺激感受性チャネルPiezo1が活性化すること、Piezo1によるカルシウム流入によりPKC-Ezrin経路が活性化してミオシンが後方細胞膜に集積することが、ニューロンを後方から押す力を生じることを証明した。
また、生後発達期の小脳容積・表面積の急激な拡大に伴い、周辺組織から受けるずり応力がニューロン遊走の方向性決定に影響する可能性をin vitro実験で検証するため、異方性伸長を実現するスマートポリマーの開発を進めた。昨年度までにメタロプロテアーゼ分解性ペプチドを架橋点に有するポリエチレングリコール(PEG)ハイドロゲルを作製し、メタロプロテアーゼの添加により10%程度の伸長を誘起可能であることを明らかとしている。今年度は生後発達期の小脳容積・表面積拡大をより忠実に再現することを目的とし、PEGハイドロゲルの構造最適化による分解速度と伸長度の制御に取り組んだ。PEGの分岐構造や分子量、ペプチド架橋剤の設計および最適化により、広範な時間域(数時間~一週間)における分解制御かつ最大100%伸長を達成可能なハイドロゲル基材を得ることができた。また初期弾性率一定でありながら、異なる分解速度を示すハイドロゲル基材の作製にも成功し、弾性率と分解速度を独立して制御可能であることを明らかとした。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

マイクロ加工技術を用いた国際共同研究では、コロナ禍で往来は殆ど出来なかったが、ニューロンの新しい遊走機構の分子基盤を明らかにし、分野に大きな革新をもたらす発見があった。現在論文発表の準備を行なっている。異方性伸長を実現するスマートポリマーの開発は、生体時間に匹敵する遅緩な等方性伸長を示す基材はできつつあり、異方性伸長を示す基材の開発に着手している。

Strategy for Future Research Activity

組織伸長のずり応力が軸索伸長に与える影響は、生体適合性の等方性伸長基材が完成し次第細胞実験を行う。並行して基質の地形が軸索伸長に与える影響をパターン化基質を用いて解析しており、軸索伸長に基質の物性が与える影響を多角的に解析した結果を論文化する予定である。

Report

(4 results)
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(34 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (26 results) (of which Int'l Joint Research: 9 results,  Invited: 15 results)

  • [Int'l Joint Research] National University of Singapore(シンガポール)

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

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Modeling intestinal stem cell function with organoids2021

    • Author(s)
      Toshio Takahashi, Kazuo Fujishima, and Mineko Kengaku
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Pages: 10912-10912

    • DOI

      10.3390/ijms222010912

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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

    • DOI

      10.1242/dev.194530

    • Related Report
      2020 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cytoskeletal forces driving neuronal migration in 3D brain tissues.2022

    • Author(s)
      Mineko Kengaku
    • Organizer
      International Symposium on Development and Plasticity of Neural Systems
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞機能に関わる動的力学特性を制御可能なハイドロゲルの設計2022

    • Author(s)
      谷本梨帆、荏原充宏、宇都甲一郎
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Multiple engines driving nuclear migration in neurons during brain development.2021

    • Author(s)
      Mineko Kengaku
    • Organizer
      RIMS Workshop Mathematical Mechanobiology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ライブイメージングで解くニューロン遊走における核輸送の制御機構2021

    • Author(s)
      見学美根子
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Mechanical stress by extracellular confinement triggers a mode transition of neuronal migration.2021

    • Author(s)
      Naotaka Nakazawa, Gianluca Grenci and Mineko Kengaku
    • Organizer
      Materials, Mimics, and Microfluidics: Engineering Tools for Mechanobiology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Nesprin-2 mediates bidirectional nuclear transport through a co-dependent interplay between dynein and kinesin-1 in migrating cerebellar granule neurons.2021

    • Author(s)
      Chuying Zhou, You Kure Wu, Takahiro Fujiwara, Mineko Kengaku
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Oscillation of AMPK activity regulates mitochondrial fission and dendritic development in hippocampal neurons.2021

    • Author(s)
      初田茜、藤島和人、栗栖純子、大野伸彦、見学美根子
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 幹細胞機能操作のための酵素分解性ハイドロゲルの設計2021

    • Author(s)
      谷本梨帆、荏原充宏、宇都甲一郎
    • Organizer
      第16回ナノ・バイオメディカル学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Design of enzymatically degradable hydrogels for unraveling the dynamic mechanical response of human mesenchymal stem cells2021

    • Author(s)
      Riho Tanimoto, Mitsuhiro Ebara, Koichiro Uto
    • Organizer
      第31回日本MRS年次大会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト間葉系幹細胞の力学応答解明に向けた酵素分解性ハイドロゲルの設計2021

    • Author(s)
      谷本梨帆、荏原充宏、宇都甲一郎
    • Organizer
      第70回高分子討論会
    • Related Report
      2021 Research-status Report
  • [Presentation] Design of enzymatically degradable hydrogels for maneuvering the human mesenchymal stem cells behavior2021

    • Author(s)
      Riho Tanimoto, Mitsuhiro Ebara, Koichiro Uto
    • Organizer
      MANA International Symposium 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [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 Research-status 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 Research-status 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 Research-status 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 Research-status 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回日本発生生物年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Mechanical stress by extracellular confinement trigger a mode transition of neuronal migration.2019

    • Author(s)
      Naotaka Nakazawa, Gianluca Grenci, Mineko Kengaku
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Nuclear Migration in 3D Brain Tissue Driven by Cytoskeletal Forces.2019

    • Author(s)
      You Kure Wu, Chuying Zhou, Hiroki Umeshima, Naotaka Nakazawa and Mineko Kengaku
    • Organizer
      20th LSACJ2019-International Conference on Interdisciplinary Life Sciences
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 微小間隙を遊走するニューロンのメカノレスポンス2019

    • Author(s)
      中澤直高
    • Organizer
      メカノバイオロジー研究を学ぶ 2019
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status 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 and Mineko Kengaku
    • Organizer
      Current Trends and Future Directions of Synapse-Circuit Plasticity Research
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Mechano-responses to the extracellular environment in migratory neurons.2019

    • Author(s)
      中澤直高、Gianluca Grenci、見学美根子
    • Organizer
      日本メカノバイオロジー研究会2019
    • Related Report
      2019 Research-status Report
    • 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. Mechanisms of force generation by cytoskeletal motors during nuclear migration of developing neurons.2019

    • Author(s)
      見学美根子
    • Organizer
      第52回日本発生生物学会年会
    • Related Report
      2019 Research-status Report
    • 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 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechano-responses to the extracellular environment in migratory neurons.2019

    • Author(s)
      Naotaka Nakazawa
    • Organizer
      3rd International Symposium on Nanoarchitectonics for Mechanobiology
    • Related Report
      2018 Research-status 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 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-10-12   Modified: 2022-12-28  

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