Synergistic Activation by Glass and Pointed Promotes Neuronal Identity in the Drosophila Eye Disc

Authors

Hongsu Wang
Komal Kumar Bollepogu Raja
Kelvin Yeung
Carolyn A Morrison
Antonia Terrizzano
Alireza Khodadadi-Jamayran
Phoenix Chen
Ashley Jordan
Cornelia Fritsch
Simon G Sprecher
Graeme Mardon
Jessica E Treisman

Publication Date

8-17-2024

Journal

Nature Communications

DOI

10.1038/s41467-024-51429-z

PMID

39154080

PMCID

PMC11330500

PubMedCentral® Posted Date

8-17-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Drosophila Proteins, Transcription Factors, ErbB Receptors, Drosophila melanogaster, Signal Transduction, Gene Expression Regulation, Developmental, Neurons, DNA-Binding Proteins, Cell Differentiation, Photoreceptor Cells, Invertebrate, Eye Proteins, Imaginal Discs, Nerve Tissue Proteins, Proto-Oncogene Proteins, Receptors, Invertebrate Peptide, Differentiation, Transcriptomics, Developmental neurogenesis, Transcriptional regulatory elements

Abstract

The integration of extrinsic signaling with cell-intrinsic transcription factors can direct progenitor cells to differentiate into distinct cell fates. In the developing Drosophila eye, differentiation of photoreceptors R1-R7 requires EGFR signaling mediated by the transcription factor Pointed, and our single-cell RNA-Seq analysis shows that the same photoreceptors require the eye-specific transcription factor Glass. We find that ectopic expression of Glass and activation of EGFR signaling synergistically induce neuronal gene expression in the wing disc in a Pointed-dependent manner. Targeted DamID reveals that Glass and Pointed share many binding sites in the genome of developing photoreceptors. Comparison with transcriptomic data shows that Pointed and Glass induce photoreceptor differentiation through intermediate transcription factors, including the redundant homologs Scratch and Scrape, as well as directly activating neuronal effector genes. Our data reveal synergistic activation of a multi-layered transcriptional network as the mechanism by which EGFR signaling induces neuronal identity in Glass-expressing cells.

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