Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation

Abstract

Vascular endothelial growth factor (VEGF) is a secreted angiogenic mitogen whose target cell specificity appears to be restricted to vascular endothelial cells. Such factors are likely candidates for regulatory molecules involved in endothelial growth control. We have characterized the murine VEGF gene and have analysed its expression pattern in embryogenesis, particularly during brain angiogenesis. Analysis of cDNA clones predicted the existence of three molecular forms of VEGF which differ in size due to heterogeneity at the carboxy terminus of the protein. The predicted mature proteins consist of 120, 164 or 188 amino acid residues. Homodimers of the two lower molecular weight forms, but not of the higher molecular weight form, were secreted by COS cells transfected with the corresponding cDNAs and were equally potent in stimulating the growth of endothelial cells. During brain development, VEGF transcript levels were abundant in the ventricular neuroectoderm of embryonic and postnatal brain when endothelial cells proliferate rapidly but were reduced in the adult when endothelial cell proliferation has ceased. The temporal and spatial expression of VEGF is consistent with the hypothesis that VEGF is synthesized and released by the ventricular neuroectoderm and may induce the ingrowth of capillaries from the perineural vascular plexus. In addition to the transient expression during brain development, a persistent expression of VEGF was observed in epithelial cells adjacent to fenestrated endothelium, e.g. in choroid plexus and in kidney glomeruli. The data are consistent with a role of VEGF as a multifunctional regulator of endothelial cell growth and differentiation.

Emerging importance of molecular pathogenesis of vascular malformations in clinical practice and classifications

“…Both VEGFR-1 and VEGFR -2 are confined to endothelial cells during embryonic development. 16,17 VEGFR-2 is exclusively localized on endothelial cells, hence playing an important role in endothelial cell differentiation and vasculogenesis. 18,19 VEGFR-3 primarily regulates the development and regulation of the lymphatic system.…”

m6A Methylation Regulates Osteoblastic Differentiation and Bone Remodeling

“…In addition, m6A methylation affects bone formation through blood vessels. Previous studies have found that vascular endothelial growth factor (VEGF), including three homologous spliced variants, 120, 164, and 188, promote angiogenesis and osteogenesis (Breier et al, 1992;Wallner et al, 2015;Hu and Olsen, 2016;Tong et al, 2019). Tian et al (2019) illustrated that knockdown of METTL3 reduced the expression of VEGFA (VEGFA-164 and VEGFA -188).…”

Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor

“…Several recent observations have indicated that VEGF, as a secreted and specific mitogen for endothelial cells, may be one of the major angiogenesis inducers in vivo. For example, the expression of VEGF and its receptors accompanies angiogenesis associated with embryonic development (Breier et al, 1992) and hormonally regulated reproductive cycles (Shweiki et al, 1993). Further, in addition to promoting the growth of vascular endothelial cells and increasing vascular leakage, VEGF also induces several proteolytic enzymes including interstitial collagenase, urokinase-type plasminogen activator, and tissue-type plasminogen activator (Pepper et al, 1991).…”