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 ). 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 ). By examining the effects of gain-of-function and loss-of-function Notchalleles 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.
