The role of vascular endothelial growth factor (VEGF) in vasculogenesis, angiogenesis, and hematopoiesis in zebrafish development

Abstract

Vascular endothelial growth factor (VEGF, VEGF-A), a selective mitogen for endothelial cells is a critical factor for vascular development. Two isoforms that differ in the presence of exons 6 and 7, Vegf(165) and Vegf(121), are the dominant forms expressed in zebrafish embryo. Simultaneous overexpression of both isoforms in the embryo results in increased production of flk1, tie1, scl, and gata1 transcripts, indicating a stimulation of both endothelial and hematopoietic lineages. We also demonstrate that vegf can stimulate hematopoiesis in zebrafish by promoting the formation of terminally differentiated red blood cells. Simultaneous overexpression of both isoforms also causes ectopic vasculature and blood cells in many of the injected embryos as well as pericardial edema in later stage embryos. Overexpression of vegf also resulted in earlier onset of flk1, tie1, scl, and gata1 expression in the embryo, indicating a possible role of vegf in stimulating the differentiation of both vascular and hematopoietic lineages. Co-injection of RNAs for both isoforms results in increased expression of three of these markers over and above that observed when either RNA is singly injected and analysis of vegf expression in the notochord mutants no tail and floating head suggests that the notochord patterns the formation of the dorsal aorta by stimulating adjacent somite cells to express vegf, which in turn functions as a signal in dorsal aorta patterning. Finally, studies of vegf expression in cloche mutant indicate that vegf expression is generally independent of cloche function. These results show that in the zebrafish embryo, vegf can not only stimulate endothelial cell differentiation but also hematopoiesis. Moreover, these effects are most dramatic when both vegf isoforms are co-expressed, indicating a synergistic effect of the expression of the two forms of the VEGF protein.

phospholipase C gamma-1is required downstream ofvascular endothelial growth factorduring arterial development

“…We have found previously that exogenous Vegf induces the expression of both of these markers, although induction of ephrin-B2a requires the Notch signaling pathway, whereas induction of flk1 does not . Consistent with previous observations (Liang et al 2001;Lawson et al 2002), we find that nearly all wild-type embryos injected with vegf 121 mRNA display increased levels of flk1 expression in their trunk blood vessels (Fig. 4a,c).…”

Common mechanism of pathogenesis in various types of metastatic osteosarcoma

“…The most prominent node in the PPI networks of KHOS and KRIB was VEGFA, which is a growth factor that is activated in vasculogenesis, angiogenesis and endothelial cell growth (24). It is not only a commonly upregulated angiogenic factor during tumor growth, but also the most frequent lymphangiogenic factor contributing to the lymphatic metastasis (25).…”

The effects of hypoxia on the expression of vascular endothelialgrowth factor in broiler lung fibroblasts

“…VEGF is an important autocrine growth factor contributing to development of the circulatory system (vasculogenesis) and the formation of blood vessels (angiogenesis) (5,15) and improvement of the pulmonary capillary beds and the blood/air barrier in the lungs (16). Physiologically, immunohistochemical staining of pulmonary parenchymal cells with VEGF has been shown as essential to keep a balance between microvascular permeability and endothelial cells (6).…”