A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye

Cell. 2005 Dec 29;123(7):1267-77. doi: 10.1016/j.cell.2005.10.040.


A critical question about signal transduction is how weak or transient activation of signaling pathways achieves a robust and long-term switch in gene expression. We report that a microRNA is part of a mechanism that makes cells sensitive to signals in the Drosophila eye. Expression of miR-7 is activated in cells as they begin differentiating into photoreceptors. This is dependent on EGF receptor (EGFR) signaling that triggers ERK-mediated degradation of the transcription factor Yan. In nonstimulated cells, Yan represses miR-7 transcription, whereas miR-7 RNA represses Yan protein expression in photoreceptors, by binding to sequences within its mRNA 3'UTR. We propose that reciprocal negative feedback between Yan and miR-7 ensures mutually exclusive expression, with Yan in progenitor cells and miR-7 in photoreceptor cells. Expression is switched when EGFR signaling transiently triggers Yan degradation. This two-tiered mechanism explains how signal transduction activity can robustly generate a stable change in gene-expression patterns.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation*
  • Conserved Sequence
  • Drosophila
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / metabolism
  • ErbB Receptors / metabolism*
  • Eye / cytology*
  • Eye Proteins / antagonists & inhibitors
  • Eye Proteins / metabolism
  • Genome
  • MicroRNAs / metabolism*
  • MicroRNAs / pharmacology
  • Models, Biological
  • Mutation
  • Photoreceptor Cells / chemistry
  • Photoreceptor Cells / cytology*
  • Photoreceptor Cells / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Time Factors
  • Transcription, Genetic


  • AOP protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • MicroRNAs
  • Repressor Proteins
  • ErbB Receptors