A study on the regulation of nuclear mechanics and DNA damage protection in neuronal migration
| Project/Area Number |
18K14819
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Kindai University (2022)
Kyoto University (2018-2021) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(6 results)
Research Products
(21 results)
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[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
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Journal Title
bioRxiv
Volume: -
Pages: 504704-504704
DOI
Related Report
Open Access
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