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 determ...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-10, Vol.275 (43), p.33679-33687
Main Authors: Lee, Sang Hoon, Schloss, Derrick J., Swain, Judith L.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Blotting, Western
Cell Movement
Cells, Cultured
Embryo, Mammalian - blood supply
Humans
Mice
Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Receptors, Fibroblast Growth Factor - genetics
Receptors, Fibroblast Growth Factor - physiology
Transgenes
Yolk Sac - blood supply
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M004994200