PUBLICATION

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
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.

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