ZFIN ID: ZDB-PUB-110317-47
A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish
Fish, J.E., Wythe, J.D., Xiao, T., Bruneau, B.G., Stainier, D.Y., Srivastava, D., and Woo, S.
Date: 2011
Source: Development (Cambridge, England)   138(7): 1409-1419 (Journal)
Registered Authors: Stainier, Didier, Woo, Stephanie, Wythe, Joshua, Xiao, Tong
Keywords: Slit/Robo, Vegf, MicroRNA, Heart tube formation, Zebrafish
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
PubMed: 21385766 Full text @ Development
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.