miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish
- Authors
- Stahlhut, C., Suárez, Y., Lu, J., Mishima, Y., and Giraldez, A.J.
- ID
- ZDB-PUB-121121-33
- Date
- 2012
- Source
- Development (Cambridge, England) 139(23): 4356-4365 (Journal)
- Registered Authors
- Giraldez, Antonio, Mishima, Yuichiro, Stahlhut, Carlos
- Keywords
- angiogenesis, microRNA, miR-1, miR-206, VEGF
- MeSH Terms
-
- Animals
- Cell Communication
- Cell Differentiation
- Cell Line
- Endothelial Cells/metabolism
- Human Umbilical Vein Endothelial Cells
- Humans
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Neovascularization, Physiologic*
- Signal Transduction
- Vascular Endothelial Growth Factor A/biosynthesis
- Vascular Endothelial Growth Factor A/metabolism*
- Zebrafish/embryology
- Zebrafish/metabolism
- PubMed
- 23132244 Full text @ Development
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.