Notch activation of yan expression is antagonized by RTK/pointed signaling in the Drosophila eye

Margaret Rohrbaugh1, Edward Ramos, Duc Nguyen

  • 1Department of Biochemistry and Molecular Biology, University Park, PA 16802, USA.

Current Biology : CB
|April 9, 2002
PubMed

Insights

Notch and Receptor Tyrosine Kinase (RTK) signaling pathways use the Yan gene to control cell fate. Yan acts as a common target, with Notch activating it and RTK repressing it via competing transcription factors.

Area of Science:

  • Developmental biology
  • Molecular genetics
  • Cell signaling

Background:

  • Receptor tyrosine kinase (RTK) and Notch signaling pathways regulate cell fate decisions.
  • While genetic interactions are known, molecular mechanisms of RTK-Notch interplay remain unclear.
  • Yan, an Ets transcriptional repressor, inhibits cell specification and differentiation.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which RTK and Notch signaling pathways interact.
  • To investigate the role of Yan as a target in Drosophila eye development.
  • To understand how Yan integrates opposing signals from RTK and Notch pathways.

Main Methods:

  • Analysis of gene expression in Drosophila eye development.
  • Identification of transcription factor binding sites on the yan enhancer.
  • In vitro DNA binding assays for Suppressor of Hairless (Su[H]) and Pointed (Pnt).

Main Results:

  • Yan is a direct transcriptional target of Notch signaling via Suppressor of Hairless (Su[H]).
  • Yan expression is repressed by the RTK pathway component Pointed (Pnt).
  • Su(H) and Pnt compete for binding to the yan enhancer, demonstrating opposing pathway regulation.

Conclusions:

  • Yan acts as a crucial integrator of opposing Notch and RTK signaling pathways.
  • The competition between Su(H) and Pnt on the yan enhancer provides a molecular mechanism for signal antagonism.
  • This study reveals how Yan mediates cell fate decisions by responding to distinct signaling inputs.

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