A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling

Dev Biol. 2014 Jan 15;385(2):263-78. doi: 10.1016/j.ydbio.2013.11.002. Epub 2013 Nov 14.

Abstract

The biochemical regulatory network downstream of receptor tyrosine kinase (RTK) signaling is controlled by two opposing ETS family members: the transcriptional activator Pointed (Pnt) and the transcriptional repressor Yan. A bistable switch model has been invoked to explain how pathway activation can drive differentiation by shifting the system from a high-Yan/low-Pnt activity state to a low-Yan/high-Pnt activity state. Although the model explains yan and pnt loss-of-function phenotypes in several different cell types, how Yan and Pointed protein expression dynamics contribute to these and other developmental transitions remains poorly understood. Toward this goal we have used a functional GFP-tagged Pnt transgene (Pnt-GFP) to perform a comparative study of Yan and Pnt protein expression throughout Drosophila development. Consistent with the prevailing model of the Pnt-Yan network, we found numerous instances where Pnt-GFP and Yan adopt a mutually exclusive pattern of expression. However we also observed many examples of co-expression. While some co-expression occurred in cells where RTK signaling is presumed low, other co-expression occurred in cells with high RTK signaling. The instances of co-expressed Yan and Pnt-GFP in tissues with high RTK signaling cannot be explained by the current model, and thus they provide important contexts for future investigation of how context-specific differences in RTK signaling, network topology, or responsiveness to other signaling inputs, affect the transcriptional response.

Keywords: Drosophila; EGFR signaling; ETS transcription factor; Embryo; Gene regulation; Imaginal discs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / embryology
  • Eye Proteins / genetics*
  • Green Fluorescent Proteins / genetics
  • Nerve Tissue Proteins / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Repressor Proteins / genetics*
  • Signal Transduction*
  • Transcription Factors / genetics*
  • Transcription, Genetic*

Substances

  • AOP protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Transcription Factors
  • pnt protein, Drosophila
  • Green Fluorescent Proteins
  • Receptor Protein-Tyrosine Kinases