Sequential activation of ETS proteins provides a sustained transcriptional response to EGFR signaling

Development. 2013 Jul;140(13):2746-54. doi: 10.1242/dev.093138.


How signal transduction, which is dynamic and fluctuating by nature, is converted into a stable trancriptional response, is an unanswered question in developmental biology. Two ETS-domain transcription factors encoded by the pointed (pnt) locus, PntP1 and PntP2, are universal downstream mediators of EGFR-based signaling in Drosophila. Full disruption of pnt function in developing eye imaginal discs reveals a photoreceptor recruitment phenotype, in which only the R8 photoreceptor cell type is specified within ommatidia. Specific disruption of either pntP1 or pntP2 resulted in the same R8-only phenotype, demonstrating that both Pnt isoforms are essential for photoreceptor recruitment. We show that the two Pnt protein forms are activated in a sequential manner within the EGFR signaling pathway: MAPK phosphorylates and activates PntP2, which in turn induces pntP1 transcription. Once expressed, PntP1 is constitutively active and sufficient to induce target genes essential for photoreceptor development. Pulse-chase experiments indicate that PntP1 is stable for several hours in the eye disc. Sequential ETS-protein recruitment therefore allows sustained induction of target genes, beyond the transient activation of EGFR.

Keywords: EGFR signaling; ETS proteins; Eye development; MAP kinase; Pointed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • pnt protein, Drosophila
  • ErbB Receptors