| Project/Area Number |
23K23887
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| Project/Area Number (Other) |
22H02624 (2022-2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2022-2023) |
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| Section | 一般 |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Phng LiKun 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, チームリーダー (70794098)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2024: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2023: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2022: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Keywords | Endothelial cell / Actin cytoskeleton / Blood vessel remodeling / Haemodynamic forces / Mechanobiology / Blood vessels / Morphogenesis / endothelial cell / actin cytoskeleton / mechanobiology / hemodynamic forces / Hemodynamic forces / Blood vessel remodelling / blood vessels / morphogenesis |
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| Outline of Research at the Start |
The generation of a hierarchical network of larger arteries and veins and smaller capillaries of optimal vessel density is achieved through vessel remodeling, which is regulated by haemodynamic forces. Here, we seek to unravel how haemodynamic forces remodel EC actomyosin organization and junctions to regulate EC behaviors and control blood vessel diameter in the zebrafish.
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| Outline of Annual Research Achievements |
We have previously discovered that endothelial cells (ECs) generate different actin organizations - circumferential, mesh and longitudinal - during vessel remodelling of intersegmental vessels in the zebrafish. The manipulation of actin organization through overexpressing Wasb or ArpC specifically in ECs resulted in a decrease in circumferential and an increase in mesh actin organization, as well as an increase in vessel diameter. Time-lapse imaging shows a correlation between circumferential actin formation and vessel constriction. Additionally, laser ablation of actin cables revealed tension in circumferential but not mesh actin. Our findings therefore suggest a role of circumferential actin in generating forces that drive vessel constriction.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Some experiments are technically challenging and require a lot of time, but we are slowly getting results.
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| Strategy for Future Research Activity |
1)Determine the contribution of myosin II activity in driving cell shape changes.
This will be investigated by inducing single cell expression of dominant negative RhoA and Myl9b specifically in ECs at then perform cell shape analysis at 2, 3 and 4 dpf.
2)Determine whether vascular malformations are caused be defective actin cytoskeleton remodelling. This will be investigated by investigating actin cytoskeleton organization and EC shape transitions in a zebrafish model of cerebral carvenous malformations (CCM).
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