2023 Fiscal Year Annual Research Report
Control of endothelial cell mechanics and blood vessels remodeling by blood flow
| Project/Area Number |
22H02624
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| Allocation Type | Single-year Grants |
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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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| Keywords | Endothelial cell / Actin cytoskeleton / Blood vessels / Morphogenesis |
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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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