MYC/MAX balance dictates cell progenitor fate by altering the HOX program in the Drosophila eye
7 affiliations
- 1Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- 2University of Ghent, Campus UZ, Ghent, Belgium
- 3IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
- 4Centre National de la Recherche Scientifique, Illkirch, France
- 5Institut National de la Santé et de la Recherche Médicale, Illkirch, France
- 6Université de Strasbourg, Illkirch, France
- 7Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) AOUBO Sant’Orsola - Laboratory of Preclinical and Translational Research in Oncology (PRO), Bologna, Italy
Abstract
The transcription factor MYC acts canonically as heterodimer with MAX to promote growth, proliferation, and metabolic adaptation. Although MYC and MAX relative levels are normally kept in balance under physiological conditions, those levels are often dysregulated in many human cancers where MYC is overexpressed and MAX can sometimes be reduced. How altered stoichiometry of MYC/MAX can impact on cell biology is not completely understood. Using the Drosophila eye amenable to genetic modifications, we demonstrate that the relative abundance of the fly MYC ortholog Myc and its partner Max affect progenitor cell fate. Elevating the Myc/Max ratio—through Myc or human MYCN overexpression, Max depletion, or combined manipulations—disrupts photoreceptor differentiation and ectopically induces the thoracic HOX gene Antennapedia within the eye disc. When such a ratio is driven to an extreme degree, the change in cell fate results in eye-to-wing transdetermination. Conversely, restoring Max levels rescues these phenotypes, demonstrating that stoichiometry, not absolute MYC levels, shapes the response. Transcriptomic profiling reveals global repression of eye-specific regulators (e.g., eyegone and prospero) and ectopic activation of wing determinants (e.g., vestigial and nubbin) while genetic interactions identify the cephalic HOX gene Deformed as a key mediator modulating MYC-dependent identity changes. Our findings uncover MYC/MAX imbalance as a developmental switch that can rewire HOX expression and reprogram progenitor identity, suggesting a conserved mechanism underlying MYC-driven cellular plasticity in cancer.
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BibTeX
@article{monticelli2026mycmax,
title = {{MYC/MAX balance dictates cell progenitor fate by altering the HOX program in the Drosophila eye}},
author = {Sara Monticelli and Giorgio Milazzo and Suleman Khan Zadran and Martina Santulli and Nicola Balboni and Silvia Strocchi and Ettore De Giorgio and Pieter Mestdagh and Angela Giangrande and Angela Giangrande and Angela Giangrande and Angela Giangrande and Roberto Bernardoni and Giovanni Perini and Giovanni Perini},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1958701},
url = {https://doi.org/10.3389/fcell.2026.1958701},
note = {CC BY},
}
RIS
TY - JOUR
TI - MYC/MAX balance dictates cell progenitor fate by altering the HOX program in the Drosophila eye
AU - Sara Monticelli
AU - Giorgio Milazzo
AU - Suleman Khan Zadran
AU - Martina Santulli
AU - Nicola Balboni
AU - Silvia Strocchi
AU - Ettore De Giorgio
AU - Pieter Mestdagh
AU - Angela Giangrande
AU - Angela Giangrande
AU - Angela Giangrande
AU - Angela Giangrande
AU - Roberto Bernardoni
AU - Giovanni Perini
AU - Giovanni Perini
PY - 2026
DA - 2026/10/26
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1958701
UR - https://doi.org/10.3389/fcell.2026.1958701
AB - The transcription factor MYC acts canonically as heterodimer with MAX to promote growth, proliferation, and metabolic adaptation. Although MYC and MAX relative levels are normally kept in balance under physiological conditions, those levels are often dysregulated in many human cancers where MYC is overexpressed and MAX can sometimes be reduced. How altered stoichiometry of MYC/MAX can impact on cell biology is not completely understood. Using the Drosophila eye amenable to genetic modifications, we demonstrate that the relative abundance of the fly MYC ortholog Myc and its partner Max affect progenitor cell fate. Elevating the Myc/Max ratio—through Myc or human MYCN overexpression, Max depletion, or combined manipulations—disrupts photoreceptor differentiation and ectopically induces the thoracic HOX gene Antennapedia within the eye disc. When such a ratio is driven to an extreme degree, the change in cell fate results in eye-to-wing transdetermination. Conversely, restoring Max levels rescues these phenotypes, demonstrating that stoichiometry, not absolute MYC levels, shapes the response. Transcriptomic profiling reveals global repression of eye-specific regulators (e.g., eyegone and prospero) and ectopic activation of wing determinants (e.g., vestigial and nubbin) while genetic interactions identify the cephalic HOX gene Deformed as a key mediator modulating MYC-dependent identity changes. Our findings uncover MYC/MAX imbalance as a developmental switch that can rewire HOX expression and reprogram progenitor identity, suggesting a conserved mechanism underlying MYC-driven cellular plasticity in cancer.
SN - 2296-634X
ER -