Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis
Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis
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DOI：
10.1242/dev.048785
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发表时间：
2010-09-15
期刊：
影响因子：
4.6
通讯作者：
Essner, Jeffrey J.
中科院分区：
文献类型：
--
作者：
Wang, Ying;Kaiser, Mark S.;Essner, Jeffrey J.
在血管生成和血管生成过程中，内皮管生成是功能性血管形成的关键步骤。在这里，我们使用表达β-肌动蛋白、α-连环蛋白和ERM家族成员Moesin 1（Moesin a）的荧光融合蛋白的活斑马鱼胚胎的体内成像，来定义一种发生在肾小管形成初始阶段的新型脊髓中空过程。段间血管（ISVs）在胚胎中。我们发现，在胚胎血管生成过程中，初级管腔沿着至少两个内皮细胞之间的沿着细胞连接处伸长。Moesin 1-EGFP在类似于细胞内空泡的结构周围富集，其在初级管腔扩张期间与管腔膜融合。对沉默心脏突变胚胎的分析表明，ISV中的初始管腔形成不依赖于血流;然而，新形成的管腔的稳定性依赖于血流。斑马鱼Moesin 1敲除和细胞移植实验表明，Moesin 1是体内管腔形成所需的ISV的内皮细胞。我们的分析表明，Moesin 1有助于维持顶/基底细胞极性的ISV定义的粘附连接。敲低粘附连接蛋白Ve-钙粘蛋白以细胞自主方式破坏顶膜和管腔的形成。我们认为，Ve钙粘蛋白和Moesin 1的功能，以建立和维持顶端/基底极性在多细胞腔形成的ISV。
Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of beta-Actin, alpha-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis. Moesin1-EGFP is enriched around structures that resemble intracellular vacuoles, which fuse with the luminal membrane during expansion of the primary lumen. Analysis of silent heart mutant embryos shows that initial lumen formation in the ISVs is not dependent on blood flow; however, stabilization of a newly formed lumen is dependent upon blood flow. Zebrafish moesin1 knockdown and cell transplantation experiments demonstrate that Moesin1 is required in the endothelial cells of the ISVs for in vivo lumen formation. Our analyses suggest that Moesin1 contributes to the maintenance of apical/basal cell polarity of the ISVs as defined by adherens junctions. Knockdown of the adherens junction protein Ve-cadherin disrupts formation of the apical membrane and lumen in a cell-autonomous manner. We suggest that Ve-cadherin and Moesin1 function to establish and maintain apical/basal polarity during multicellular lumen formation in the ISVs.