| Project/Area Number |
16K14584
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya City University (2017-2018)
National Institute for Physiological Sciences (2016) |
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Principal Investigator |
Shimizu Takeshi 名古屋市立大学, 大学院医学研究科, 講師 (60398237)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | オリゴデンドロサイト / メカノセンサー / 機械刺激 / メカノバイオロジー |
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| Outline of Final Research Achievements |
Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. The molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that the mechanosensor p130Cas and YAP respond to mechanical stress within OL lineage cells, and control OL morphogenesis and maturation.In addition, in order to investigate when mechanical stresses influence OLs during developmental stages, we have prepared a traction force biosensor and have conducted research to visualize the traction force loaded in OL cells.The traction force sensor probe uses fluorescence resonance energy transfer (FRET) system.Since FRET is highly sensitive to the distance between the fluorophores, FRET efficiency decreases by the loading of traction force in OL cells.
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| Academic Significance and Societal Importance of the Research Achievements |
生体の恒常性の維持や個体発生に関わる因子として、メカニカルストレスは非常に重要な役割を果たしていると考えられる。本研究では、中枢神経系の構成細胞の中でも力学的な影響が大きいと考えられるOLに着目した。その結果、メカニカルストレスが、OLの形態形成と成熟を制御することを明らかにした。従来の液性因子シグナルとは性質が異なる細胞外の物理的な環境が重要な役割を果たすことを明らかにすることにより、中枢神経系の形成に関わる新しい学術的な知見や、神経疾患に関わる新規タンパク質の作用機序を明らかにできる可能性がある。
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