Work

MYC/MAX balance dictates cell progenitor fate by altering the HOX program in the Drosophila eye

Year: 2026

Type: article

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.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1958701