Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor.
Basic fibroblast growth factor (FGF)-2 is important for vessel formation and/or maintenance of vascular integrity in the embryo. FGF signaling may be mediated through transmembrane tyrosine kinase receptors or directly through intracellular pathways that do not involve receptor activation. To determine the role of receptor-mediated signaling in endothelial cells, an adenovirus encoding truncated FGF receptor (FGFR)-1, under the control of the cytomegalovirus promoter, was expressed in endothelial cells. FGF signaling was impaired, as indicated by inhibition of MAPK phosphorylation. Functional consequences included inhibition of endothelial cell migration and induction of apoptosis. To address the role of endothelial FGFR signaling in vascular development, recombinant adenovirus encoding a dominant-negative FGFR was injected into the sinus venosus of embryonic day 9.0 cultured mouse embryos. Previous studies demonstrated that transgenes delivered via adenovirus, under the control of the cytomegalovirus promoter, are expressed selectively in the developing vasculature. Embryos expressing a control adenovirus developed normally, whereas those expressing the FGFR-1 mutant exhibited abnormal embryonic and extra-embryonic vascular development. These data demonstrate that FGF, by signaling through the FGFR, plays a pivotal role in the development and maintenance of a mature vascular network in the embryo.
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5109, USA.
S H
SH
Lee
D J
DJ
Schloss
J L
JL
Swain
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000098:blood supply*; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D019076:Transgenes; D015017:Yolk Sac / Q000098:blood supply
D017468:Receptors, Fibroblast Growth Factor; D020928:Mitogen-Activated Protein Kinases