Selective regulation of arterial branching morphogenesis by synectin
Selective regulation of arterial branching morphogenesis by synectin
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DOI：
10.1016/j.devcel.2006.03.012
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发表时间：
2006-06-01
影响因子：
11.8
通讯作者：
Simons, Michael
中科院分区：
文献类型：
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作者：
Chittenden, Thomas W.;Claes, Filip;Simons, Michael
分枝形态发生是维管网络形成的关键过程。迄今为止，很少有人知道有关的分子事件调节这一过程。我们调查了参与这个过程中的连接蛋白。在斑马鱼胚胎中，由于成血管细胞和动脉内皮细胞的迁移和增殖受损，而不影响静脉发育，导致粘连蛋白敲低的背主动脉发育不全，分支少，发育不良，和薄的体间血管。Synectin（-/-）小鼠表现出身体和器官尺寸减小，动脉数量减少，多个血管床中动脉分支模式改变，而静脉系统保持正常。小鼠粘连蛋白（-/-）的主要动脉，但不是静脉，内皮细胞表现出减少在体外管的形成，迁移和增殖和受损的极化，由于异常定位的激活Rac 1。我们的结论是，参与选择性调节动脉，但不是静脉，生长和分支形态发生，Rac 1在这个过程中发挥了重要作用。
Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.