Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
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DOI：
10.1038/embor.2011.194
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发表时间：
2011-11-01
期刊：
影响因子：
7.7
通讯作者：
Gerhardt, Holger
中科院分区：
文献类型：
--
作者：
Stenzel, Denise;Franco, Claudio A.;Gerhardt, Holger
血管基底膜的各个成分如何影响内皮细胞行为仍不清楚。在这里，我们发现层粘连蛋白 α 4 (Lama4) 通过诱导体内内皮 Dll4/Notch 信号传导来调节尖端细胞数量和血管密度。 Lama4 缺陷导致小鼠视网膜中 Dll4 表达减少、丝状伪足和尖端细胞形成过多，从而表现出 Dll4/Notch 抑制的效果。 Lama4 介导的 Dll4 表达需要体外整合素和体内整合素 β1 的组合。我们得出的结论是，适当的层粘连蛋白/整合素诱导的信号传导对于诱导 Dll4 表达的生理功能水平和调节体内萌芽血管生成过程中的分支频率是必要的。
How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin alpha 4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin beta 1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.