Dynamic endothelial cell rearrangements drive developmental vessel regression.
Dynamic endothelial cell rearrangements drive developmental vessel regression.
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DOI：
10.1371/journal.pbio.1002125
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发表时间：
2015-04
期刊：
影响因子：
9.8
通讯作者：
Gerhardt H
中科院分区：
文献类型：
--
作者：
Franco CA;Jones ML;Bernabeu MO;Geudens I;Mathivet T;Rosa A;Lopes FM;Lima AP;Ragab A;Collins RT;Phng LK;Coveney PV;Gerhardt H
功能性血管网络的图案化通过修剪多余的连接来实现。血管退化的细胞和分子原理知之甚少。在这里，我们表明，回归介导的动态和极化迁移的内皮细胞，代表吻合反向。建立并分析了重塑血管网络中所有内皮细胞的第一轴向极性图，我们提出细胞的平衡运动在低剪切条件下维持原始丛处于亚稳态动态。我们预测，流动诱导的极化迁移的内皮细胞打破对称性，并导致稳定的高流量/剪切段和相邻的低流量/剪切段的回归。一项对小鼠视网膜和斑马鱼血管系统的研究显示了不同的血流模式如何指导内皮细胞的定向和迁移，作为稳定或修剪单个血管段的机制。血管网络如何实现其分支模式的问题是我们理解器官形成以及涉及血管异常的疾病的关键。功能性血管分支模式需要血管片段的回归（或修剪）;然而，对此的分子基础知之甚少。在这里，我们研究了小鼠视网膜和斑马鱼血管网络的重塑，并重点关注内皮细胞的细胞成分-血管内衬的细胞层。我们使用高分辨率成像来绘制和分析血管重塑过程中内皮细胞方向与血流方向的关系。我们确定了通过内皮细胞迁移表征血管消退的顺序步骤，没有发现预测视网膜内皮细胞死亡的证据。将内皮细胞映射与流动诱导的剪切力的计算建模相结合，允许对驱动血管重塑的内皮细胞迁移模式进行系统级预测。我们的工作建立了血流的局部差异如何驱动内皮细胞定向和逆着血流方向迁移。我们发现，动态和极化迁移的内皮细胞导致的回归节段低流量和稳定的节段高流量下。我们提出，强流功能作为一个“吸引器”的内皮细胞，而灌注不良的血管是不太“吸引力”，从而促进非功能性血管节段的回归。
Patterning of functional blood vessel networks is achieved by pruning of superfluous connections. The cellular and molecular principles of vessel regression are poorly understood. Here we show that regression is mediated by dynamic and polarized migration of endothelial cells, representing anastomosis in reverse. Establishing and analyzing the first axial polarity map of all endothelial cells in a remodeling vascular network, we propose that balanced movement of cells maintains the primitive plexus under low shear conditions in a metastable dynamic state. We predict that flow-induced polarized migration of endothelial cells breaks symmetry and leads to stabilization of high flow/shear segments and regression of adjacent low flow/shear segments. A study of mouse retina and zebrafish vasculature shows how differential blood flow patterns direct the orientation and migration of endothelial cells as a mechanism for stabilizing or pruning individual blood vessel segments. The question of how blood vessel networks achieve their branching patterns is key to our understanding of organ formation as well as diseases that involve vascular anomalies. Regression (or pruning) of blood vessel segments is required for functional vascular branching patterns; however, the molecular basis for this is poorly understood. Here we investigate remodeling of vascular networks in the mouse retina and in zebrafish and focus on the cellular components of the endothelium—the cell layer that lines blood vessels. We use high-resolution imaging to map and analyze endothelial cell orientation in relation to blood flow direction during vascular remodeling. We identify sequential steps that characterize blood vessel regression through endothelial cell migration, finding no evidence for predicted endothelial cell death in the retina. Combining endothelial cell mapping with computational modeling of flow-induced shear forces allows a systems-level prediction of endothelial cell migration patterns that drive vascular remodeling. Our work establishes how local differences in blood flow drive endothelial cells to orientate and migrate against the direction of flow. We show that the dynamic and polarized migration of endothelial cells leads to the regression of segments under low flow and the stabilization of segments under high flow. We propose that strong flow functions as an “attractor” for endothelial cells, while poorly perfused vessels are less “attractive,” thereby promoting regression of non-functional vessel segments.
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影响因子：
9.8
作者：
Chen Q;Jiang L;Li C;Hu D;Bu JW;Cai D;Du JL
通讯作者：
Du JL
影响因子：
11.8
作者：
Phng LK;Potente M;Leslie JD;Babbage J;Nyqvist D;Lobov I;Ondr JK;Rao S;Lang RA;Thurston G;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
11.4
作者：
Martin, Maud;Geudens, Ilse;Dequiedt, Franck
通讯作者：
Dequiedt, Franck
影响因子：
9.2
作者：
Herwig, Lukas;Blum, Yannick;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
4.6
作者：
le Noble, F;Moyon, D;Eichmann, A
通讯作者：
Eichmann, A