First published online October 24, 2008
Development 135, 2204e (2008)
© The Company of Biologists Limited
Signals for a good blood supply
The body's organs and tissues depend on a functional vasculature to supply
them with nutrients and oxygen. Now, two papers in Development shed
light on the signalling pathways that control the development of this
essential blood vessel network.
In the first study, Christof Niehrs and colleagues identify R-spondin 3
(Rspo3; an activator of Wnt/β-catenin signalling) as a novel,
evolutionarily conserved angiogenic factor in embryogenesis (see
p. 3655). In
vertebrate embryos, blood cells and vascular endothelial cells develop from
bi-potent haemangioblasts, but the factors that control haemangioblast fate
remain largely unknown. Niehrs' team now shows that Rspo3, which is expressed
in blood-forming organs, regulates the balance between endothelial and
haematopoietic differentiation in Xenopus embryos by promoting the
specification of blood-vessel-forming angioblasts and inhibiting
haematopoietic (blood-cell) specification. They also report that targeted
disruption of Rspo3 in mouse embryos causes lethal vascular defects,
and that R-spondin signalling promotes proliferation and sprouting
angiogenesis in human endothelial cells in vitro. Finally, the researchers
show that Rspo3 triggers Wnt/β-catenin signalling to induce the
expression of VEGF (which promotes endothelial differentiation), indicating
for the first time that Wnt and VEGF signalling function in an integrated
pathway that enhances angiogenesis.
In the second paper, Rong Wang and colleagues reveal that Notch and ephrin
B2/EphB4 signalling play important but different roles in the development of a
functional vasculature. Both pathways, they report, coordinate the sizes of
arteries and veins formed during angiogenesis and consequently ensure that
proper interfaces form between them (see
p. 3755). By
examining the effects of gain-of-function and loss-of-function Notch
alleles in mouse embryos, Wang's team shows that Notch signalling promotes
arterial specification, which controls the proportion of arterial to venous
endothelial cells and thus regulates the relative sizes of the developing
dorsal aorta and cardinal vein. Disruption of ephrin B2/EphB4 signalling also
alters the relative sizes of these vessels, they report, but by causing
endothelial cells with venous identity to mislocalise into the aorta. Overall,
these results suggest that the Notch and ephrin B2/EphB4 signalling pathways
are both essential for balanced ateriovenous development during blood vessel
formation.
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Related articles in Development:
- The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development
- Olga Kazanskaya, Bisei Ohkawara, Melanie Heroult, Wei Wu, Nicole Maltry, Hellmut G. Augustin, and Christof Niehrs
Development 2008 135: 3655-3664.
[Abstract]
[Full Text]
- Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis
- Yung Hae Kim, Huiqing Hu, Salvador Guevara-Gallardo, Michael T. Y. Lam, Shun-Yin Fong, and Rong A. Wang
Development 2008 135: 3755-3764.
[Abstract]
[Full Text]
