Werner Risau´s work had a decisive impact on defining the overall nature of neovascularization processes during embryonic development. Accordingly, neovascularization occurs either by vasculogenesis, when a new capillary network is laid down by endothelial precursor cells differentiating in situ or alternatively by angiogenesis, when new capillaries are invading the organ by forming vascular sprouts that originate from pre-existing vessels.
Werner Risau very successfully propagated the concept that the same factors, which are essential for the formation of blood vessels during embryonic development, also influence pathological angiogenesis during tumor growth. Among the many pioneering contributions that he made to our current understanding of the mechanisms responsible for blood vessel development are studies on the role of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) as well as their receptors, during the vascularization of certain organs, such as the embryonic kidney and brain.
Selected reading:
• Risau W, Developing brain produces an angiogenesis factor. Proc Natl Acad Sci U S A 1986 83(11):3855-3859
• Risau W, Ekblom P. Production of a heparin-binding angiogenesis factor by the embryonic kidney. J Cell Biol 1986 103:1101-1107
• Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T. Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 1988 102(3):471-478
• Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992 114(2):521-32.
• Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992 359:845-848.
• Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 1993 72(6):835-46.
• Ikeda E, Achen MG, Breier G, Risau W. Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 1995 270(34):19761-19766
• Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995 11:73-91.
• Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996 380(6573):435-439.
• Risau W, Mechanisms of angiogenesis. Nature 1997 386:671-674
• Marti HH, Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15809-14.