Endothelial cell self-fusion during vascular pruning.
Endothelial cell self-fusion during vascular pruning.
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DOI：
10.1371/journal.pbio.1002126
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发表时间：
2015-04
期刊：
影响因子：
9.8
通讯作者：
Affolter M
中科院分区：
文献类型：
--
作者：
Lenard A;Daetwyler S;Betz C;Ellertsdottir E;Belting HG;Huisken J;Affolter M
在胚胎发育过程中，血管网络重塑，以满足日益增长的组织对氧气和营养物质的需求。这是通过修剪多余的血管段来实现的，然后允许更有效的血流模式。由于缺乏适用于高分辨率实时成像的体内系统，修剪过程的动力学尚未详细描述。在这里，我们提出了一种新的模型，研究修剪在细胞水平上的斑马鱼胚胎的肠下静脉（SIV）丛。我们表明，血管退化是一个协调的过程中，涉及管腔塌陷和细胞-细胞接触决议的细胞重排。有趣的是，修剪过程中的细胞重排类似于血管融合过程中的内皮细胞行为，顺序相反。在修剪节段中，内皮细胞首先向它们加入亲本血管分支的相对侧迁移，从而将多细胞节段重塑为单细胞连接。通常，在整个过程中维持管腔，并且通过细胞自我融合形成瞬时单细胞管。在第二步中，单细胞连接被单侧解决，并且修剪细胞重新加入相对的分支。因此，我们第一次表明，各种细胞活动的协调，以实现血管修剪和定义两个不同的形态发生途径，这是由流动环境选择。斑马鱼胚胎的活体成像揭示了修剪不需要的血管所涉及的多种细胞活动，包括内皮细胞的自我融合。血管系统将气体、营养物质、激素和代谢物循环到身体的所有器官。它是生存所必需的，并且在胚胎发育的早期阶段就已经发挥作用。此时，新血管的形成主要是通过血管生成--新血管从现有血管中生长出来。新的血管芽相互连接，形成具有血流的功能环，这一过程称为吻合。以这种方式形成的血管丛随后重塑为具有有效流动模式的最终结构。重构通常涉及修剪或回归不必要的分支，从而简化网络。我们在斑马鱼胚胎中的修剪过程的活体成像研究表明，血管退化通过细胞重排发生，其中细胞连续迁移出修剪分支。结果，最初的多细胞血管被减少到单个细胞连接，当最后一个细胞并入相邻的分支时，该连接最终被解决。如果管腔保持在修剪容器中，则该过程涉及通过细胞自我融合瞬时形成单细胞管。因此，我们展示了各种细胞活动是如何协调的，以实现血管修剪。
During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell–cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment. In vivo live imaging of zebrafish embryos reveals the diverse cellular activities involved in the pruning of unwanted blood vessels, including the self-fusion of endothelial cells. The blood vasculature circulates gas, nutrients, hormones, and metabolites to all organs of the body. It is indispensable for survival and already functions at very early stages of embryonic development. At this point, new blood vessels form mainly through angiogenesis—the outgrowth of new vessels from existing ones. New vascular sprouts connect to each other to form functional loops with blood flow, a process termed anastomosis. Vascular plexuses formed in this way subsequently remodel to a final structure with efficient flow patterns. Remodeling often involves pruning or regression of unnecessary branches, leading to a simplification of the network. Our in vivo live imaging studies of the pruning process in the zebrafish embryo show that vessel regression occurs through cell rearrangements, wherein cells consecutively migrate out of the pruning branch. As a result, the initially multicellular vessel is reduced to a single cell connection that is eventually resolved when the last cell incorporates into the neighboring branch. If the lumen is maintained in the pruning vessel, the process involves transient formation of a unicellular tube through cell self-fusion. Thus, we show how a variety of cellular activities are coordinated to achieve vessel pruning.
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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：
2.7
作者：
Blum, Yannick;Belting, Heinz-Georg;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
9.8
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
通讯作者：
Gerhardt H
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Korn, Claudia;Scholz, Beate;Augustin, Iris
通讯作者：
Augustin, Iris