Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo.
Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo.
复制标题
血流在体内血管生成期间通过膜膨胀而导致管腔形成。
DOI：
10.1038/ncb3320
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发表时间：
2016-04
影响因子：
21.3
通讯作者：
Gerhardt H
中科院分区：
文献类型：
--
作者：
Gebala V;Collins R;Geudens I;Phng LK;Gerhardt H
血管如何构建、维持和适应持续灌注的管腔以满足局部代谢需求仍然知之甚少。最近的研究表明，血流本身在血管网络的重塑中起着至关重要的作用，并表明它也是新血管连接的腔化所必需的。然而，目前尚不清楚在血管形态发生过程中血流动力学如何促进新血管腔的形成。在这里，我们报告说，在体内萌芽血管生成过程中，血流通过诱导内皮细胞顶膜的球形变形来驱动管腔扩张，这一过程我们称为逆起泡。我们发现，内皮细胞通过肌动球蛋白的局部和瞬时募集和收缩来对这些膜侵入做出反应，并且这种机制是血管生成芽中单向管腔扩张所必需的。我们的工作将反膜起泡确定为细胞对高外部压力的反应。我们表明，就血管而言，这种膜动力学可以驱动整体组织形态发生所需的局部细胞形状变化，从而揭示脊椎动物管腔形成的压力驱动机制。
How vascular tubes build, maintain and adapt continuously perfused lumens to meet local metabolic needs remains poorly understood. Recent studies showed that blood flow itself plays a critical role in the remodelling of vascular networks, and suggested it is also required for lumenisation of new vascular connections. However, it is still unknown how haemodynamic forces contribute to the formation of new vascular lumens during blood vessel morphogenesis. Here we report that blood flow drives lumen expansion during sprouting angiogenesis in vivo by inducing spherical deformations of the apical membrane of endothelial cells, in a process that we termed inverse blebbing. We show that endothelial cells react to these membrane intrusions by local and transient recruitment and contraction of actomyosin, and that this mechanism is required for single, unidirectional lumen expansion in angiogenic sprouts. Our work identifies inverse membrane blebbing as a cellular response to high external pressure. We show that in the case of blood vessels such membrane dynamics can drive local cell shape changes required for global tissue morphogenesis, shedding light on a pressure-driven mechanism of lumen formation in vertebrates.
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