Sugden Wade W, Meissner Robert, Aegerter-Wilmsen Tinri, Tsaryk Roman, Leonard Elvin V, Bussmann Jeroen, Hamm Mailin J, Herzog Wiebke, Jin Yi, Jakobsson Lars, Denz Cornelia, Siekmann Arndt F
Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, D-48149 Muenster, Germany.
Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Muenster, D-48149 Muenster, Germany.
Nat Cell Biol. 2017 Jun;19(6):653-665. doi: 10.1038/ncb3528. Epub 2017 May 22.
The hierarchical organization of properly sized blood vessels ensures the correct distribution of blood to all organs of the body, and is controlled via haemodynamic cues. In current concepts, an endothelium-dependent shear stress set point causes blood vessel enlargement in response to higher flow rates, while lower flow would lead to blood vessel narrowing, thereby establishing homeostasis. We show that during zebrafish embryonic development increases in flow, after an initial expansion of blood vessel diameters, eventually lead to vessel contraction. This is mediated via endothelial cell shape changes. We identify the transforming growth factor beta co-receptor endoglin as an important player in this process. Endoglin mutant cells and blood vessels continue to enlarge in response to flow increases, thus exacerbating pre-existing embryonic arterial-venous shunts. Together, our data suggest that cell shape changes in response to biophysical cues act as an underlying principle allowing for the ordered patterning of tubular organs.
大小合适的血管的分层组织确保血液正确分配到身体的所有器官，并通过血流动力学线索进行控制。在当前概念中，内皮依赖性切应力设定点会导致血管在流速较高时扩张，而较低的流速会导致血管变窄，从而建立体内平衡。我们发现，在斑马鱼胚胎发育过程中，血管直径最初扩张后，血流增加最终会导致血管收缩。这是通过内皮细胞形状变化介导的。我们确定转化生长因子β共受体内皮糖蛋白是这一过程中的重要参与者。内皮糖蛋白突变细胞和血管在血流增加时会继续扩张，从而加剧先前存在的胚胎动静脉分流。总之，我们的数据表明，细胞对生物物理线索做出的形状变化是一种基本原则，可实现管状器官的有序模式形成。
