| 研究課題/領域番号 |
23K23887
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| 補助金の研究課題番号 |
22H02624 (2022-2023)
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| 研究種目 |
基盤研究(B)
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| 配分区分 | 基金 (2024)
補助金 (2022-2023) |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分44010:細胞生物学関連
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
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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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2024年度)
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| 配分額 *注記 |
17,550千円 (直接経費: 13,500千円、間接経費: 4,050千円)
2024年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
2023年度: 6,760千円 (直接経費: 5,200千円、間接経費: 1,560千円)
2022年度: 8,320千円 (直接経費: 6,400千円、間接経費: 1,920千円)
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| キーワード | 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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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Some experiments are technically challenging and require a lot of time, but we are slowly getting results.
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| 今後の研究の推進方策 |
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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