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

http://www.ncbi.nlm.nih.gov/pubmed/21385766

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 RIS Download

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

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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:

ZFIN (Data, Gene Expression)

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