Cellular communication across tissues is an essential process during embryonic development. Secreted factors with potent morphogenetic
activity are key elements of this cross-talk, and precise regulation of their expression is required to elicit appropriate
physiological responses. MicroRNAs (miRNAs) are versatile post-transcriptional modulators of gene expression. However, the
large number of putative targets for each miRNA hinders the identification of physiologically relevant miRNA-target interactions.
Here we show that miR-1 and miR-206 negatively regulate angiogenesis during zebrafish development. Using target protectors,
our results indicate that miR-1/206 directly regulate the levels of Vascular endothelial growth factor A (VegfA) in muscle,
controlling the strength of angiogenic signaling to the endothelium. Conversely, reducing the levels of VegfAa, but not VegfAb,
rescued the increase in angiogenesis observed when miR-1/206 were knocked down. These findings uncover a novel function for
miR-1/206 in the control of developmental angiogenesis through the regulation of VegfA, and identify a key role for miRNAs
as regulators of cross-tissue signaling.