Defective vascular morphogenesis and mid-gestation embryonic death in mice lacking RA-GEF-1.
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.
Wei
Ping
P
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.
Satoh
Takaya
T
Edamatsu
Hironori
H
Aiba
Atsu
A
Setsu
Tomiyoshi
T
Terashima
Toshio
T
Kitazawa
Sohei
S
Nakao
Kazuki
K
Yoshikawa
Yoko
Y
Tamada
Masako
M
Kataoka
Tohru
T
D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities* / Q000378:metabolism*; D020964:Embryo Loss / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D005865:Gestational Age; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009389:Neovascularization, Pathologic / Q000196:embryology* / Q000378:metabolism*