2021 Fiscal Year Final Research Report
Functional analysis of nodal cilia derived calcium influx in left-right symmetry breaking
| Project/Area Number |
19K06753
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 44040:Morphology and anatomical structure-related
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| Research Institution | University of Fukui (2020-2021)
Institute of Physical and Chemical Research (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 繊毛 / ダイニン / 左右 / カルシウム |
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| Outline of Final Research Achievements |
The Left and Right in human body is determined by the function of nodal cilia. Immotile cilia sense extracellular signals but if Ca2+ plays a role in flow sensing had been unclear. Here, I examined the role of ciliary Ca2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca2+ transients were detected in the crown cells at the node. These Ca2+ transients showed L-R asymmetry. It was also shown that cytoplasmic Ca2+ transients could leak into the cilioplasm and it was necessary to distinguish between ciliary Ca2+ influx and cell bodied derived Ca2+ transients in cilia. I could show the existence of ciliary Ca2+ influx in the absence of cytoplasmic Ca2+ transients with drug treatment. Furthermore, suppression of intraciliary Ca2+ transients delayed L-R symmetry breaking. These results indicate cilium-derived Ca2+ transients in crown cells in the initiation of L-R symmetry breaking.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
体の左右決定は内蔵逆位、内臓錯位などの原因となり、重篤な心臓病の原因ともなることから、医学的に重要である。一方で、これまで、繊毛が流れを感知するメカニズムなど、不明な部分が多く残されている。特に、繊毛による物理的シグナルの感知とカルシウムシグナルの関係は、これを否定する論文が報告されるなど、決定的な証拠は得られていなかった。本研究では、これまで観測されてこなかった左右決定に関わる繊毛内でのカルシウム濃度変化を初めて、イメージングにより捉えることに成功した。これは、上記の理由から、今後の繊毛研究において重要な知見である。
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