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Updated: Jun 27, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
The Notch and Epidermal Growth Factor Receptor (EGFR) pathways both regulate proliferation and differentiation, and the cellular response to each is often influenced by the other. Here, we describe a mechanism that links them in a sequential fashion, in the developing compound eye of Drosophila. EGFR activation induces photoreceptor (R cell) differentiation and promotes their expression of Delta. This Notch ligand then induces neighboring cells to become nonneuronal cone cells. ebi and strawberry notch (sno) regulate EGFR-dependent Delta transcription by antagonizing a repressor function of Suppressor of Hairless (Su(H)). Sno binds to Su(H), and Ebi, an F-box/WD40 protein, forms a complex with Su(H) and the corepressor SMRTER. EGFR-activated transcriptional derepression requires ebi and sno, is proteasome-dependent, and correlates with the translocation of SMRTER to the cytoplasm.
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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