Development, Vol 114, Issue 2 521-532, Copyright © 1992 by Company of Biologists

JOURNAL ARTICLES

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

G Breier, U Albrecht, S Sterrer and W Risau
Max-Planck-Institut fur Psychiatrie, Martinsried, FRG.

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.
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				H. J. H. Marti, M. Bernaudin, A. Bellail, H. Schoch, M. Euler, E. Petit, and W. Risau Hypoxia-Induced Vascular Endothelial Growth Factor Expression Precedes Neovascularization after Cerebral Ischemia Am. J. Pathol., March 1, 2000; 156(3): 965 - 976. [Abstract] [Full Text] [PDF]

				L.-W. Wu, L. D. Mayo, J. D. Dunbar, K. M. Kessler, O. N. Ozes, R. S. Warren, and D. B. Donner VRAP Is an Adaptor Protein That Binds KDR, a Receptor for Vascular Endothelial Cell Growth Factor J. Biol. Chem., February 25, 2000; 275(9): 6059 - 6062. [Abstract] [Full Text] [PDF]

				L.-W. Wu, L. D. Mayo, J. D. Dunbar, K. M. Kessler, M. R. Baerwald, E. A. Jaffe, D. Wang, R. S. Warren, and D. B. Donner Utilization of Distinct Signaling Pathways by Receptors for Vascular Endothelial Cell Growth Factor and Other Mitogens in the Induction of Endothelial Cell Proliferation J. Biol. Chem., February 18, 2000; 275(7): 5096 - 5103. [Abstract] [Full Text] [PDF]

				P. Helbling, D. Saulnier, and A. Brandli The receptor tyrosine kinase EphB4 and ephrin-B ligands restrict angiogenic growth of embryonic veins in Xenopus laevis Development, January 1, 2000; 127(2): 269 - 278. [Abstract] [PDF]

				S. A. Stacker, A. Vitali, C. Caesar, T. Domagala, L. C. Groenen, E. Nice, M. G. Achen, and A. F. Wilks A Mutant Form of Vascular Endothelial Growth Factor (VEGF) That Lacks VEGF Receptor-2 Activation Retains the Ability to Induce Vascular Permeability J. Biol. Chem., December 3, 1999; 274(49): 34884 - 34892. [Abstract] [Full Text] [PDF]

				Y. Seko, Y. Seko, H. Fujikura, J. Pang, T. Tokoro, and H. Shimokawa Induction of Vascular Endothelial Growth Factor After Application of Mechanical Stress to Retinal Pigment Epithelium of the Rat In Vitro Invest. Ophthalmol. Vis. Sci., December 1, 1999; 40(13): 3287 - 3291. [Abstract] [Full Text] [PDF]

				S. FRANK, B. STALLMEYER, H. KÄMPFER, N. KOLB, and J. PFEILSCHIFTER Nitric oxide triggers enhanced induction of vascular endothelial growth factor expression in cultured keratinocytes (HaCaT) and during cutaneous wound repair FASEB J, November 1, 1999; 13(14): 2002 - 2014. [Abstract] [Full Text]

				P. N. Bernatchez, S. Soker, and M. G. Sirois Vascular Endothelial Growth Factor Effect on Endothelial Cell Proliferation, Migration, and Platelet-activating Factor Synthesis Is Flk-1-dependent J. Biol. Chem., October 22, 1999; 274(43): 31047 - 31054. [Abstract] [Full Text] [PDF]

				F. DOCAGNE, O. NICOLE, H. H. MARTI, E. T. MacKENZIE, A. BUISSON, and D. VIVIEN Transforming growth factor-{beta}1 as a regulator of the serpins/t-PA axis in cerebral ischemia FASEB J, August 1, 1999; 13(11): 1315 - 1324. [Abstract] [Full Text]

				H. T. YUAN, C. SURI, G. D. YANCOPOULOS, and A. S. WOOLF Expression of Angiopoietin-1, Angiopoietin-2, and the Tie-2 Receptor Tyrosine Kinase during Mouse Kidney Maturation J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1722 - 1736. [Abstract] [Full Text]

				D R Thickett, L Armstrong, and A B Millar Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions Thorax, August 1, 1999; 54(8): 707 - 710. [Abstract] [Full Text]

				M. Sondell, G. Lundborg, and M. Kanje Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System J. Neurosci., July 15, 1999; 19(14): 5731 - 5740. [Abstract] [Full Text] [PDF]

				G. Ascherl, C. Hohenadl, O. Schatz, E. Shumay, J. Bogner, L. Eckhart, E. Tschachler, P. Monini, B. Ensoli, and M. Sturzl Infection With Human Immunodeficiency Virus-1 Increases Expression of Vascular Endothelial Cell Growth Factor in T Cells: Implications for Acquired Immunodeficiency Syndrome-Associated Vasculopathy Blood, June 15, 1999; 93(12): 4232 - 4241. [Abstract] [Full Text] [PDF]

				J. S. Krussel, E. M. Casan, F. Raga, J. Hirchenhain, Y. Wen, H.-Y. Huang, P. Bielfeld, and M. L. Polan Expression of mRNA for vascular endothelial growth factor transmembraneous receptors Flt1 and KDR, and the soluble recetor sflt in cycling human endometrium Mol. Hum. Reprod., May 1, 1999; 5(5): 452 - 458. [Abstract] [Full Text] [PDF]