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


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.

Pubmed ID: 21385766


  • Fish JE
  • Wythe JD
  • Xiao T
  • Bruneau BG
  • Stainier DY
  • Srivastava D
  • Woo S


Development (Cambridge, England)

Publication Data

April 9, 2011

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL54737
  • Agency: NHLBI NIH HHS, Id: P01-HL089707-01A1
  • Agency: NHLBI NIH HHS, Id: T32HL007731
  • Agency: Canadian Institutes of Health Research, Id:

Mesh Terms

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