An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch

Leo Tsuda1, Raghavendra Nagaraj, S Lawrence Zipursky

  • 1Department of Biological Chemistry and Department of Human Genetics, Molecular Biology Institute, Los Angeles, CA 90095, USA.

Cell
|September 17, 2002
PubMed

Insights

Epidermal Growth Factor Receptor (EGFR) activation in Drosophila eyes promotes Delta expression, initiating a sequence that influences cell differentiation. This process involves specific proteins and is dependent on proteasome activity.

Area of Science:

  • Developmental Biology
  • Cell Signaling

Background:

  • The Notch and Epidermal Growth Factor Receptor (EGFR) pathways are crucial for cell proliferation and differentiation.
  • Cross-talk between these pathways significantly influences cellular responses.
  • Understanding their interplay is key to deciphering developmental processes.

Purpose of the Study:

  • To elucidate the mechanism linking EGFR and Notch signaling in Drosophila eye development.
  • To identify the sequential events initiated by EGFR activation that impact downstream signaling.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism for studying developmental pathways.
  • Investigated gene expression and protein interactions related to EGFR and Notch signaling.
  • Employed genetic and proteasome inhibition assays to understand regulatory mechanisms.

Main Results:

  • EGFR activation in developing Drosophila eyes leads to photoreceptor differentiation and Delta ligand expression.
  • Delta, induced by EGFR, subsequently signals to neighboring cells, promoting their differentiation into cone cells.
  • The proteins ebi and strawberry notch (sno) are essential for EGFR-dependent Delta transcription by modulating Suppressor of Hairless (Su(H)) activity.
  • EGFR-mediated transcriptional derepression is proteasome-dependent and involves SMRTER cytoplasmic translocation.

Conclusions:

  • A sequential signaling cascade links EGFR and Notch pathways in Drosophila eye development.
  • EGFR signaling initiates a process that culminates in Notch-mediated cell fate decisions.
  • The interplay of ebi, sno, Su(H), and SMRTER is critical for regulating this EGFR-dependent transcriptional control.

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