Secreted signalling molecules regulate cellular communication across tissues during development. For example, during angiogenesis in zebrafish embryos, vascular endothelial growth factor (VEGF) secreted by muscle controls the expansion and remodelling of the vascular network. The precise regulation of VEGF expression in muscle cells is therefore essential for angiogenesis but how is this regulation achieved? On p 4356, Yuichiro Mishima, Antonio Giraldez and colleagues report that miR-1 and miR-206 (miR-1/206; two conserved microRNAs with similar sequences) negatively regulate angiogenesis during zebrafish development. The negative effect of miR-1/206 on angiogenesis, the researchers report, is mediated in part by direct regulation of VegfAa in muscle. Thus, masking the target sites for miR-1/206 in the 3′ UTR of vegfaa has a pro-angiogenic effect similar to that of miR-1/206 knockdown. By contrast, reducing the levels of VegfAa rescues the increase in angiogenesis produced by miR-1/206 knockdown. Together, these findings uncover a novel function for miR-1/206 in the control of developmental angiogenesis and highlight a key role for microRNAs as regulators of cross-tissue signalling.