The role of FGF and VEGF in angioblast induction and migration during vascular development

Abstract

The embryonic vasculature forms by the processes of vasculogenesis and angiogenesis. Angioblasts (endothelial cell precursors) appear to be induced by fibroblast growth factor 2 (FGF‐2). The angioblasts contributing to the dorsal aortae arise by an epithelial to mesenchymal transformation of cells originating from the splanchnic mesoderm. QH‐l and vascular endothelial growth factor receptor 2 (VEGFR‐2) both appear to label these cells as they adopt a mesenchymal morphology. Since VEGFR‐2 is the earliest known VEGF receptor this suggests that VEGF is not involved in angioblast induction. VEGF does appear to be critical, however, for growth and morphogenesis of angioblasts into the initial vascular pattern. Controlled delivery of FGF‐2 from beads and aggregates of cells transfected with quail VEGF have been used in our laboratory to study the role of these growth factors in angioblast induction and migration. We have induced cells from the epithelial quail somite to differentiate into angioblasts with FGF‐2 both in the embryo and in culture. This is a useful model system to study the origins of endothelial cells that are normally more diffusely induced during gastrulation by an obscure process probably involving signals from the embryonic endoderm. The origins of arterial versus venous endothelial cells is also poorly understood but recent findings on the distribution of ephrins and Eph receptors suggest that molecular differences exist prior to the onset of circulation. Finally, studies on the role of growth factors in such diverse phenomena as stem cell biology, angiogenesis, and molecular medicine in addition to vascular development suggest multiple roles for FGF‐2 and VEGF in vascular development. © 2001 Wiley‐Liss, Inc.

Better vascular engraftment and function in pancreatic islets transplanted without prior culture

“…In an attempt to explain why freshly isolated islets become more efficiently revascularised than cultured islets following transplantation, we measured concentrations of angiogenic factors in freshly isolated and cultured rat islets, as well as in 4-day-old and 1-month-old rat islet grafts. The process of angiogenesis has been extensively studied in different experimental setups, and the most important growth factors involved seem to be VEGF and bFGF [32][33][34]. Consistent with previous studies [35,36], we found that the islet production of VEGF increased markedly during culture.…”

Possible involvement of protein kinase C activation in differentiation of human umbilical vein endothelium‐derived cell into smooth muscle‐like cell

“…Fibroblast growth factors (FGFs) play key roles in the induction of both angioblasts (Poole et al, 2001) and haemangioblasts (Poole et al, 2001;Cox and Poole, 2000) from the mesoderm, and most endothelial precursors divide and differentiate in response to vascular endothelial growth factor (VEGF) (Raffi, 2000;Isner and Asahara, 1999). Although the above is true in general, several studies have suggested that SMC-like cells can arise from atrio-ventricular and dorsal aorta ECs (Arciniegas et al, 1992;DeRuitar et al, 1997;Nakajima et al, 1997;Frid et al, 2002).…”

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…As stated above, the phenotype of fgfr knockout mice is scarcely informative even though adenovirus-drive dominant-negative FGFR1 expression leads to severe vascular alterations in mouse embryos [76]. Also, FGF2 promotes the proliferation and differentiation of VEGFR-2 + hemangioblast precursors from the mesoderm [114]. In embryoid bodies, embryonic stem cells can differentiate into a variety of cell lineages, including endothelial cells [115].…”