Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development
Journal of cell science, 2004•journals.biologists.com
We have employed embryoid bodies derived from murine embryonal stem cells to study
effects on vascular development induced by fibroblast growth factor (FGF)-2 and FGF
receptor-1, in comparison to the established angiogenic factor vascular endothelial growth
factor (VEGF)-A and its receptor VEGF receptor-2. Exogenous FGF-2 promoted formation of
morphologically distinct, long slender vessels in the embryoid bodies, whereas VEGF-A-
treated bodies displayed a compact plexus of capillaries. FGF-2 stimulation of embryonal …
effects on vascular development induced by fibroblast growth factor (FGF)-2 and FGF
receptor-1, in comparison to the established angiogenic factor vascular endothelial growth
factor (VEGF)-A and its receptor VEGF receptor-2. Exogenous FGF-2 promoted formation of
morphologically distinct, long slender vessels in the embryoid bodies, whereas VEGF-A-
treated bodies displayed a compact plexus of capillaries. FGF-2 stimulation of embryonal …
We have employed embryoid bodies derived from murine embryonal stem cells to study effects on vascular development induced by fibroblast growth factor (FGF)-2 and FGF receptor-1, in comparison to the established angiogenic factor vascular endothelial growth factor (VEGF)-A and its receptor VEGF receptor-2. Exogenous FGF-2 promoted formation of morphologically distinct, long slender vessels in the embryoid bodies, whereas VEGF-A-treated bodies displayed a compact plexus of capillaries. FGF-2 stimulation of embryonal stem cells under conditions where VEGF-A/VEGFR-2 function was blocked, led to formation of endothelial cell clusters, which failed to develop into vessels. FGFR-1-/- embryoid bodies responded to VEGF-A by establishment of the characteristic vascular plexus, but FGF-2 had no effect on vascular development in the absence of FGFR-1. The FGFR-1-/- embryoid bodies displayed considerably increased basal level of vessel formation, detected by immunohistochemical staining for platelet-endothelial cell adhesion molecule (PECAM)/CD31. This basal vascularization was blocked by neutralizing antibodies against VEGFR-2 or VEGF-A and biochemical analyses indicated changes in regulation of VEGFR-2 in the absence of FGFR-1 expression. We conclude that VEGF-A/VEGFR-2-dependent vessel formation occurs in the absence of FGF-2/FGFR-1, which, however, serve to modulate vascular development.
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