PUBLICATION

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

Authors
Fish, J.E., Wythe, J.D., Xiao, T., Bruneau, B.G., Stainier, D.Y., Srivastava, D., and Woo, S.
ID
ZDB-PUB-110317-47
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
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.
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