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.