VEGF Regulates Cell Behavior during Vasculogenesis

Department of Cell Biology and the Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston 29425, USA.
Developmental Biology (Impact Factor: 3.55). 09/2000; 224(2):178-88. DOI: 10.1006/dbio.2000.9744
Source: PubMed


Prominent among molecules that control neovascular processes is vascular endothelial growth factor (VEGF). The VEGF ligands comprise a family of well-studied mitogens/permeability factors that bind cell surface receptor tyrosine kinases. Targets include VEGF receptor-1/Flt1 and VEGF receptor-2/Flk1. Mice lacking genes for VEGF ligand or VEGF receptor-2 die early in gestation, making it difficult to determine the precise nature of underlying endothelial cellular behavior(s). To examine the effect(s) of VEGF signaling on cell behavior in detail, we conducted loss-of-function studies using avian embryos. Injection of soluble VEGFR-1 results in malformed vascular networks and the absence of large vessels. In the most severe cases embryos exhibited vascular atresia. Closely associated with the altered phenotype was a clear endothelial cell response-a marked decrease in cell protrusive activity. Further, we demonstrate that VEGF gain of function strikingly increased cell protrusive activity. Together, our data show that VEGF/VEGF receptor signaling regulates endothelial cell protrusive activity, a key determinant of blood vessel morphogenesis. We propose that VEGF functions as an instructive molecule during de novo blood vessel morphogenesis.

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Available from: Christopher J Drake
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    • "Vascular endothelial growth factor-A (VEGF-A) is a potent vascular endothelial cell (EC)-specific mitogen that stimulates EC proliferation , migration and angiogenesis, and it has also been shown to improve EC function and survival in vitro as well as vascular reactivity in vivo [1] [2] [3]. The actions of VEGF-A are primarily mediated through its two major tyrosine kinase receptors, namely VEGF receptor-1 (VEGFR-1, also known as fms-like tyrosine kinase; Flt1) and VEGF receptor-2 (VEGFR-2, also known as kinase insert domain receptor; KDR) [4]. "
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    • "Previous studies have shown the Hh can activate several signaling pathways relevant to endothelial cell patterning and behavior, including the VEGF and Notch pathways (Pola et al., 2001; Lawson et al., 2002). Indeed, VEGF is known to regulate the density of filopodial extensions on ECs (Ruhrberg et al., 2002; Gerhardt et al., 2003) and inhibition of VEGF activity results in reduction of cellular protrusions during vascular plexus formation (Drake et al., 2000), consistent with the results we observed. Preliminary results (Fig. 6A–C) indicate that VEGF transcript levels are responsive to changes in Hh signaling . "
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