Distinct Cellular Mechanisms of Blood Vessel Fusion in the Zebrafish Embryo
Distinct Cellular Mechanisms of Blood Vessel Fusion in the Zebrafish Embryo
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DOI：
10.1016/j.cub.2011.10.016
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发表时间：
2011-11-22
期刊：
影响因子：
9.2
通讯作者：
Affolter, Markus
中科院分区：
文献类型：
--
作者：
Herwig, Lukas;Blum, Yannick;Affolter, Markus
虽然许多血管生成的细胞和分子机制已被深入研究[1]，但对血管吻合的基础过程知之甚少。我们已经产生了表达连接蛋白封闭带1（ZO 1）的GFP标记版本的转基因鱼系，以可视化体内血管融合和管腔形成过程中发生的单个细胞行为。这些生命观察表明，内皮细胞（EC）使用两种不同的形态发生机制，细胞膜内陷和索中空产生不同类型的血管管。在吻合的初始步骤期间，在细胞接触的初始位点处形成的细胞连接扩展成环，产生顶端膜隔室的细胞界面，如顶端标记物足糖萼蛋白-2（Pdxl 2）的定位所定义。在脊髓中空化过程中，这些顶端膜隔室通过细胞重排和广泛的连接重塑聚集在一起，导致管腔合并并形成多细胞管。通过膜内陷的血管融合发生在近端至远端方向上的预先存在的管腔附近，并且是血流依赖性的。在这里，内陷的内细胞膜经历伴随的顶基底极化，并且血管腔由穿过EC的跨细胞腔的延伸形成，其形成单细胞或无缝管。
Although many of the cellular and molecular mechanisms of angiogenesis have been intensely studied [1], little is known about the processes that underlie vascular anastomosis. We have generated transgenic fish lines expressing an EGFP-tagged version of the junctional protein zona occludens 1 (ZO1) to visualize individual cell behaviors that occur during vessel fusion and lumen formation in vivo. These life observations show that endothelial cells (ECs) use two distinct morphogenetic mechanisms, cell membrane invagination and cord hollowing to generate different types of vascular tubes. During initial steps of anastomosis, cell junctions that have formed at the initial site of cell contacts expand into rings, generating a cellular interface of apical membrane compartments, as defined by the localization of the apical marker podocalyxin-2 (Pdxl2). During the cord hollowing process, these apical membrane compartments are brought together via cell rearrangements and extensive junctional remodeling, resulting in lumen coalescence and formation of a multicellular tube. Vessel fusion by membrane invagination occurs adjacent to a preexisting lumen in a proximal to distal direction and is blood-flow dependent. Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube.