Traditionally, blood vessels are regarded as an inert network of tubes that supply tissues with nutrients and oxygen, but recent studies suggest that blood vessels play perfusion-independent roles in early development. Now, on p. , Eli Keshet and co-workers report that blood vessels also determine the reproducible branch pattern of lung airways in mice. During lung development, the coordinated branching of epithelial and vascular tubes culminates in their co-alignment in the mature organ. By ablating the lung vasculature in vivo and in lung explants, the researchers show that, although the first two-dimensional round of epithelial branching proceeds at a nearly normal rate, branching events that require rotation to change the branching plane into the third dimension are selectively affected. This role of the vasculature is independent of perfusion, flow or blood-borne substances but can be partly explained by perturbation of the expression of stereospecific branching regulators such as FGF10. Together, these results reveal a novel perfusion-independent role for the vasculature in directing three-dimensional organogenesis.
