Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1
Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1
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DOI：
10.1016/j.bbrc.2009.07.108
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发表时间：
2009-10-02
影响因子：
3.1
通讯作者：
Kataoka, Tohru
中科院分区：
文献类型：
--
作者：
Kanemura, Hoshimi;Satoh, Takaya;Kataoka, Tohru
RA-GEF-1是一个鸟嘌呤核苷酸交换因子的小GTdR ap 1。RA-GEF-1基因敲除小鼠在移植后约7.5天开始显示血管发育缺陷，并在移植后9.5天死亡。在这里，我们采用体外培养系统的尿囊外植体和内皮细胞，以获得深入了解的机制RA-GEF-1介导的调控胚胎血管网络的形成。在RA-GEF-1基因敲除的尿囊和卵黄囊中，血管丛的发育和VE-钙粘蛋白在细胞-细胞连接处的积累显著受损。RA-GEF-1基因敲除也减少了激活特异性探针观察到的Rap 1激活。由于缺乏RA-GEF-1，VE-钙粘蛋白在细胞-细胞连接处的积累减少，体外血管形成缺陷被组成性激活的Rap 1的异位表达抑制。总之，这些结果表明RA-GEF-1下游的Rap 1参与调节小鼠胚胎中血管网络的形成。(C)2009 Elsevier Inc. All rights reserved.
RA-GEF-1 is a guanine nucleotide exchange factor for the small GTPase Rap1. RA-GEF-1 knockout mice show defects in vascular development starting around 7.5 days post coitum and die by 9.5 days post coitum. Here, we employed in vitro culture systems for allantois explants and endothelial cells to gain insights into the mechanism for RA-GEF-1-mediated regulation of embryonic vascular network formation. The development of the vascular plexus and the accumulation of VE-cadherin at cell-cell junctions were significantly impaired in the RA-GEF-1 knockout allantois and yolk sac. Rap1 activation as visualized by an activation-specific probe was also diminished by RA-GEF-1 knockout. Reduced accumulation of VE-cadherin at cell-cell junctions and defects in blood vessel formation in vitro due to the lack of RA-GEF-1 were suppressed by ectopic expression of constitutively activated Rap1. Overall, these results suggest the involvement of Rap1 downstream of RA-GEF-1 in the regulation of vascular network formation in mouse embryos. (C) 2009 Elsevier Inc. All rights reserved.