The netrins are well-known neural guidance cues that can also direct blood vessel growth. But the exact role of netrin 1 signalling in angiogenesis has been under debate, with it being reported to have both anti-angiogenic and angiogenic effects. To help resolve this issue, Dean Li's lab has now conditionally inactivated the netrin receptor gene Unc5b specifically in the embryonic endothelium of mice (see p. 659). The only detectable vascular abnormality in Unc5b mutant embryos, they report,is a reduced number of placental labyrinthine arterioles, which leads to increased placental resistance and to a fatal reversal of flow in the umbilical artery. This phenotype cannot be rescued by wild-type trophectoderm(from which extra-embryonic placental tissues derive), showing that UNC5B-mediated signalling is a specific component of fetal placental angiogenesis. The knockdown of Unc5b in zebrafish revealed a similarly pro-angiogenic role, causing the specific loss of the parachordal blood vessel. From their results, the authors suggest that UNC5B/netrin signalling could be implicated in clinical uteroplacental insufficiency.