Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Curr Biol. 2011 Nov 22;21(22):1942-8. doi: 10.1016/j.cub.2011.10.016. Epub 2011 Nov 10.
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.
尽管血管生成的许多细胞和分子机制已经被深入研究[1]，但对于血管吻合过程背后的机制知之甚少。我们已经生成了表达 EGFP 标记的连接蛋白 zona occludens 1（ZO1）的转基因鱼系，以可视化体内血管融合和管腔形成过程中单个细胞的行为。这些活体观察表明，内皮细胞（ECs）使用两种不同的形态发生机制，细胞膜内陷和索状中空化，生成不同类型的血管管腔。在吻合的初始步骤中，在细胞接触的初始部位形成的细胞连接扩展成环状，形成一个由顶端标记蛋白 podocalyxin-2（Pdxl2）定位定义的顶端膜区室的细胞界面。在索状中空化过程中，通过细胞重排和广泛的连接重塑，这些顶端膜区室被拉近，导致管腔融合和多细胞管腔的形成。通过细胞膜内陷进行的血管融合发生在近端到远端的预先存在的管腔旁边，并且依赖于血流。在这里，内陷的内细胞膜同时经历顶端到基底的极化，血管管腔通过穿过 EC 的细胞内管腔的延伸形成，形成单细胞或无缝管腔。
