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Publication : Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1.

First Author  Kanemura H Year  2009
Journal  Biochem Biophys Res Commun Volume  387
Issue  4 Pages  754-9
PubMed ID  19635461 Mgi Jnum  J:152727
Mgi Id  MGI:4359570 Doi  10.1016/j.bbrc.2009.07.108
Citation  Kanemura H, et al. (2009) Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1. Biochem Biophys Res Commun 387(4):754-9
abstractText  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.
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