Wei Ping, Satoh Takaya, Edamatsu Hironori, Aiba Atsu, Setsu Tomiyoshi, Terashima Toshio, Kitazawa Sohei, Nakao Kazuki, Yoshikawa Yoko, Tamada Masako, Kataoka Tohru
Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Biochem Biophys Res Commun. 2007 Nov 9;363(1):106-12. doi: 10.1016/j.bbrc.2007.08.149. Epub 2007 Sep 10.
A multitude of guanine nucleotide exchange factors (GEFs) regulate Rap1 small GTPases, however, their individual functions remain obscure. Here, we investigate the in vivo function of the Rap1 GEF RA-GEF-1. The expression of RA-GEF-1 in wild-type mice starts at embryonic day (E) 8.5, and continues thereafter. RA-GEF-1(-/-) mice appear normal until E7.5, but become grossly abnormal and dead by E9.5. This mid-gestation death appears to be closely associated with severe defects in yolk sac blood vessel formation. RA-GEF-1(-/-) yolk sacs form apparently normal blood islands by E8.5, but the blood islands fail to coalesce into a primary vascular plexus, indicating that vasculogenesis is impaired. Furthermore, RA-GEF-1(-/-) embryos proper show severe defects in the formation of major blood vessels. These results suggest that deficient Rap1 signaling may lead to defective vascular morphogenesis in the yolk sac and embryos proper.
众多鸟嘌呤核苷酸交换因子（GEFs）调节Rap1小GTP酶，然而，它们各自的功能仍不清楚。在这里，我们研究Rap1鸟嘌呤核苷酸交换因子1（RA-GEF-1）的体内功能。RA-GEF-1在野生型小鼠中的表达从胚胎第8.5天开始，并在之后持续。RA-GEF-1基因敲除小鼠在胚胎第7.5天之前看起来正常，但在胚胎第9.5天时变得严重异常并死亡。这种妊娠中期死亡似乎与卵黄囊血管形成的严重缺陷密切相关。RA-GEF-1基因敲除小鼠的卵黄囊在胚胎第8.5天时形成明显正常的血岛，但血岛未能融合成初级血管丛，这表明血管发生受损。此外，RA-GEF-1基因敲除的胚胎本身在主要血管形成方面存在严重缺陷。这些结果表明，Rap1信号不足可能导致卵黄囊和胚胎本身血管形态发生缺陷。
