A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish

Development. 2011 Apr;138(7):1409-19. doi: 10.1242/dev.060046.

Abstract

Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Cell Movement / physiology
  • Cell Polarity / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Heart / embryology*
  • In Situ Hybridization
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardium / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Organogenesis / physiology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism

Substances

  • Glycoproteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • roundabout protein
  • slit protein, vertebrate