title: miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510,  USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Stahlhut
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suárez
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mishima
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Giraldez
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A