Synergistic activation by Glass and Pointed promotes neuronal identity in the Drosophila eye disc

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 and Jessica E. Treisman ()
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Hongsu Wang: NYU Grossman School of Medicine
Komal Kumar Bollepogu Raja: Baylor College of Medicine
Kelvin Yeung: Baylor College of Medicine
Carolyn A. Morrison: NYU Grossman School of Medicine
Antonia Terrizzano: NYU Grossman School of Medicine
Alireza Khodadadi-Jamayran: NYU Grossman School of Medicine
Phoenix Chen: NYU Grossman School of Medicine
Ashley Jordan: NYU Grossman School of Medicine
Cornelia Fritsch: Université de Fribourg
Simon G. Sprecher: Université de Fribourg
Graeme Mardon: Baylor College of Medicine
Jessica E. Treisman: NYU Grossman School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51429-z

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