miR-1 and miR-206 Regulate Angiogenesis by Modulating VegfA Expression in Zebrafish

Development. 2012 Dec 1;139(23):4356-64. doi: 10.1242/dev.083774.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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

Substances

  • MicroRNAs
  • Vascular Endothelial Growth Factor A