Maintenance of vascular integrity in the embryo requires signaling throughthe fibroblast growth factor receptor

Basic fibroblast growth factor (FGF)-2 is important for vessel formation an d/or maintenance of vascular integrity in the embryo. FGF signaling may be mediated through transmembrane tyrosine kinase receptors or directly throug h intracellular pathways that do not involve receptor activation. To determ ine the role of receptor-mediated signaling in endothelial cells, an adenov irus encoding truncated FGF receptor (FGFR)-1, under the control of the cyt omegalovirus promoter, was expressed in endothelial cells. FGF signaling wa s impaired, as indicated by inhibition of MAPK phosphorylation, Functional consequences included inhibition of endothelial cell migration and inductio n of apoptosis. To address the role of endothelial FGFR signaling in vascul ar development, recombinant adenovirus encoding a dominant-negative FGFR wa s injected into the sinus venosus of embryonic day 9.0 cultured mouse embry os. Previous studies demonstrated that transgenes delivered via adenovirus, under the control of the cytomegalovirus promoter, are expressed selective ly in the developing vasculature, Embryos expressing a control adenovirus d eveloped normally, whereas those expressing the FGFR-1 mutant exhibited abn ormal embryonic and extra-embryonic vascular development. These data demons trate that FGF, by signaling through the FGFR, plays a pivotal role in the development and maintenance of a mature vascular network in the embryo.