| Project/Area Number |
17K15153
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Morphology/Structure
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Mizuno Katsutoshi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (00777774)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 繊毛 / カルシウム / 左右 / 左右軸 / 発生・分化 |
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| Outline of Final Research Achievements |
Left-Right (LR) asymmetry in mouse embryo is dependent on fluid flow generated by the movement of the nodal cilia. Ca2+ signals are essential for this process, however, the mechanisms were not clear. In our research, we tried to visualize and analyze the function of the ciliary Ca2+ for LR asymmetry. We generated mice that express Ca2+ indicator, GCaMP6 in embryonic cilia, and successfully observed Ca2+ transients. Also, we performed simultaneous observation of Ca2+ dynamics in cilia and in cytoplasm and detected Left-biased signal. Patterns of Ca2+ signals in mutants or embryos treated with drugs were disturbed. From those analyses, strong relationship between ciliary and cytoplasmic Ca2+ signals were suggested. We also observed the ciliary Ca2+ signal under the drug treatment to visualize direct ciliary Ca2+ influx. Position of cilia showing Ca2+ influx was biased to the left side of the node, suggesting that ciliary Ca2+ influx is responsible for the determination of LR asymmetry.
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| Academic Significance and Societal Importance of the Research Achievements |
左右軸の適切な決定は体の形作りの上で重要であり、重篤な病気となりうる繊毛病などの原因解明の観点からも医学的にも基礎的な知見の蓄積が必要とされる。左右軸の異常は先天異常へとつながることから、その機序の解明は先端医学においても基盤となり、社会的な貢献も大きい。左右の極性の起源に関してはここ二十年で急速に研究が進み、ヒトを含む多くの哺乳類で繊毛が決定的な役割を果たすことが示されてきた。一方で、繊毛と左右決定の機序に関しては依然として多くの疑問が残っている。本研究は、その中でも不明であった繊毛とカルシウム、左右決定との関わりを明確に直接的に答えたものであり、分野に大きな前進をもたらすと考えられる。
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