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A study on the regulation of nuclear mechanics and DNA damage protection in neuronal migration

Research Project

Project/Area Number 18K14819
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKindai University (2022)
Kyoto University (2018-2021)

Principal Investigator

Nakazawa Naotaka  近畿大学, 理工学部, 講師 (90800780)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsニューロン遊走 / 細胞核 / マイクロデバイス流路 / メカノバイオロジー / 弾性率 / DNA損傷
Outline of Final Research Achievements

We found that LaminA protein levels fluctuated in migratory cerebellar granule cells during cerebellum development. In addition, overexpression of LMNA in cerebellar granule cells reduced migration efficiency. These suggest that LMNA-mediated regulation of nuclear stiffness is critical for neuronal migration. On the other hand, we found that 53BP transiently aggregated in the nucleus when the migratory neurons passed through confined space. Our experiments using in vitro system and inhibitor treatment revealed that DNA damage by mechanical stress in migratory neurons was repaired by non-homologous end joining.

Academic Significance and Societal Importance of the Research Achievements

細胞の移動は脳内の神経細胞に限った現象ではなく、組織の形づくりや免疫の機能、がん転移など多くの細胞で観察される。先行研究により、人工的な条件下で上皮性がん細胞を狭い間隙の中を通過させることで、細胞核の著しい変形が起こりDNA損傷が誘引されることが報告された。これらの研究は、単純な環境における細胞の動きを報告したものであり、これまでに身体の中で同様の現象が起こるか不明であった。本研究の遂行により、からだの中のような複雑な環境下で同様の現象を検証することが可能となる。そのため、本研究は神経細胞移動の仕組みの解明にとどまらず、様々な種類の細胞が移動できる仕組みの理解に波及する可能性がある。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2023 2022 2021 2020 2019 2018 Other

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

  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] シンガポール国立大学メカノバイオロジー研究所(シンガポール)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] シンガポール国立大学メカノバイオロジー研究所(シンガポール)

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

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

    • Related Report
      2018 Research-status Report
  • [Journal Article] Editorial: Multicellularity: Views from cellular signaling and mechanics2023

    • Author(s)
      Hirata Hiroaki、Nakazawa Naotaka、Hirashima Tsuyoshi、Ravasio Andrea
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 11 Pages: 1-3

    • DOI

      10.3389/fcell.2023.1172921

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Migrating neurons adapt motility modes to brain microenvironments via a mechanosensor, PIEZO12023

    • Author(s)
      Nakazawa Naotaka、Grenci Gianluca、Kameo Yoshitaka、Takeda Noriko、Sawada Tsuyoshi、Kurisu Junko、Zhang Zhejing、Adachi Taiji、Nonomura Keiko、Kengaku Mineko
    • Journal Title

      bioRiv

      Volume: -

    • DOI

      10.1101/2023.01.17.524464

    • Related Report
      2022 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex2022

    • Author(s)
      Tanita Frey, Tomonari Murakami, Koichiro Maki, Takumi Kawaue, Ayaka Sugai, Naotaka Nakazawa, Taiji Adachi, Mineko Kengaku, Kenichi Ohki, Yukiko Gotoh, Yusuke Kishi
    • Journal Title

      bioRxiv

      Volume: - Pages: 504704-504704

    • DOI

      10.1101/2022.08.22.504704

    • Related Report
      2022 Annual Research Report
    • 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] Molecular mechanisms of mechano-sensing / -response for neuronal migration in 3D brain tissue2022

    • Author(s)
      Naotaka Nakazawa, Gianluca Grenci, Mineko Kengaku
    • Organizer
      NEURO2022
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Mechanical stress by extracellular confinement triggers a mode transition of neuronal migration2021

    • Author(s)
      Naotaka Naotaka, Gianluca Grenci, Mineko Kengaku
    • Organizer
      Materials, Mimics, and Microfluidics: Engineering tools for Mechanobiology (MBI 3M)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanical stress by extracellular confinement trigger a mode transition of neuronal migration2020

    • Author(s)
      Naotaka Naotaka, Gianluca Grenci, Mineko Kengaku
    • Organizer
      第58回日本生物物理学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Mechano-responses to the extracellular environment in migratory neurons2019

    • 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
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Mechanical stress by extracellular confinement trigger a mode transition of neuronal migration2019

    • Author(s)
      中澤直高、Gianluca Grenci, 見学美根子
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Mechano-resnponses to the extracellular environment in migratory neurons2019

    • Author(s)
      Naotaka Nakazawa, Mineko Kengaku
    • Organizer
      International Symposium on nanoarchitectonics for mechanobiology
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cellular responses to mechanical influences of the extracellular environment2018

    • Author(s)
      Naotaka Nakazawa
    • Organizer
      The Japan Society of Mechanical Engineers Hokkaido Branch-Biomechanics Research Meeting (33rd Seminar)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Nuclear mechanics in migratory cerebellar granule cells2018

    • Author(s)
      Naotaka Nakazawa, William Theoputra, Jiang Zixian, Masaki Utsunomiya, Gianluca Grenci, Shigehiro H. Yoshimura, and Mineko Kengaku
    • Organizer
      Looking to the future of Developmental Cell Biology Symposium
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] Multicellularity: Views from cellular signaling and mechanics2023

    • Author(s)
      Hiroaki Hirata, Andrea Ravasio, Naotaka Nakazawa and Tsuyoshi Hirashima
    • Total Pages
      138
    • Publisher
      Frontiers ebook
    • Related Report
      2022 Annual Research Report
  • [Book] 生体の科学 2019年08月号 (通常号) ( Vol.70 No.4)2019

    • Author(s)
      中澤直高、見学美根子
    • Total Pages
      5
    • Publisher
      医学書院
    • Related Report
      2019 Research-status Report
  • [Remarks] 中澤直高のウェブサイト

    • URL

      https://nnakazawa8.wixsite.com/nnakazawa

    • Related Report
      2019 Research-status Report
  • [Remarks] iCeMSニュースレターVol.7(特集メカノバイオロジー )

    • URL

      https://www.icems.kyoto-u.ac.jp/ja/pr/pdf/iCeMS_Our_World_Your_Future_v07_j.pdf

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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