RRC ID 12751
Author Kanemura H, Satoh T, Bilasy SE, Ueda S, Hirashima M, Kataoka T.
Title Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1.
Journal Biochem Biophys Res Commun
Abstract 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 7.5days post coitum and die by 9.5days 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.
Volume 387(4)
Pages 754-9
Published 2009-10-2
DOI 10.1016/j.bbrc.2009.07.108
PII S0006-291X(09)01469-7
PMID 19635461
MeSH Allantois / blood supply* Allantois / metabolism Animals Antigens, CD / metabolism Cadherins / metabolism Cells, Cultured Female Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / physiology* Mice Mice, Knockout Neovascularization, Physiologic / genetics* Yolk Sac / blood supply* Yolk Sac / metabolism rap1 GTP-Binding Proteins / metabolism*
IF 2.985
Times Cited 10
DNA material CSII-CMV-MCS (RDB04377) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)