Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies
Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies
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DOI：
10.1073/pnas.94.12.6273
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发表时间：
1997-06-10
影响因子：
11.1
通讯作者：
Huber, P
中科院分区：
文献类型：
--
作者：
Vittet, D;Buchou, T;Huber, P
血管内皮细胞钙粘附素(VE-cadherin，VE-cadherin)仅在内皮细胞中表达，并严格定位于细胞间连接。与钙粘蛋白家族的其他成员一样，VE-钙粘蛋白能够以钙离子依赖的方式介导同型的细胞相互作用。在小鼠胚胎中，VE-钙粘附素转录本在血管发育的最早阶段被检测到。为了确定血管内皮细胞的组装是否需要VE-cadherin的表达，我们通过基因打靶的方法获得了VE-cadherin阴性的小鼠胚胎干细胞(VE-cadherin(-/-)ES细胞)，并检测了ES来源的类胚体(EBS)对血管发育的影响。与野生型EBS相比，我们观察到VE-cadherin(-/-)ES来源的EBS中内皮细胞仍然分散，无法形成血管样图案，然而，分散的VE-cadherin(-/-)ES来源的内皮细胞表达大量其他内皮标志物。VE-钙粘蛋白基因的靶向性零突变不干扰ES细胞的造血分化潜能，这些体外实验与VE-钙粘蛋白在血管结构组装中的关键作用是一致的。
Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed in endothelial cells and is strictly located at cell-to-cell junctions. As the other members of the cadherin family, VE-cadherin is able to mediate a homotypic type of cellular interaction in a Ca2+-dependent manner. In the mouse embryo, VE-cadherin transcripts are detected at the earliest stages of vascular development. To ascertain if VE-cadherin expression is required for the assembly of endothelial cells into vascular structures, we generated VE-cadherin negative mouse embryonic stem cells (VE-cadherin(-/-) ES cells) by gene targeting and examined the consequences on vascular development of ES-derived embryoid bodies (EBs), In contrast to wild-type EBs, we observed that endothelial cells remained dispersed and failed to organize a vessel-like pattern in VE-cadherin(-/-) ES-derived EBs, However, dispersed VE-cadherin(-/-) ES-derived endothelial cells expressed a large range of other endothelial markers, Moreover, the targeted null-mutation in the VE-cadherin locus did not interfere with the hematopoietic differentiation potential of ES cells, These irt vitro experiments are consistent with a pivotal role of VE-cadherin in vascular structure assembly.