Biology subjects

De Giorgio, E.

Publications and source records attributed to De Giorgio, E..

4 recordsLinked to original sources

bioRxiv2025

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

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 dMyc and its partner dMax affect progenitor cell fate. Elevating the dMyc/dMax ratio--through dMyc or human MYCN overexpression, dMax 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 dMax 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.

developmental biology↗

bioRxiv2025

A switch in the mode of tissue growth extends the growth phase of Drosophila wing primordia during early pupal development

Understanding how final organ size is established during development raises two key questions: how organs increase their mass and how they stop growing upon reaching an appropriate size. While organ growth is driven by conserved signaling pathways, the mechanisms underlying growth arrest remain elusive. Studies on Drosophila imaginal wing discs have provided a model whereby final organ size coincides with an arrest of cell proliferation at the end of the larval phase. Here, through 3D reconstruction and volume measurements, we show that wing discs grow continuously throughout the larva-to-pupa (L/P) transition and proceed to growth arrest later during the pupal period. This supplemental growth phase involves a switch at the L/P transition that uncouples proliferation from tissue growth, with an important contribution from Insulin/IGF signaling. These findings challenge the existing model of imaginal wing development and open new avenues for our understanding of growth arrest and organ size determination.

developmental biology↗

bioRxiv2024

Different cellular and molecular mechanisms of chitin deposition contribute to the specificity of the two chitin synthases in D. melanogaster.

Chitin is a major component of arthropod extracellular matrices, including the exoskeleton and the midgut peritrophic matrix. It plays a key role in the development, growth and viability of insects. Besides the biological importance of this aminopolysaccharide, chitin also receives a lot of attention for its practical applications in medicine and biotechnology as a superior biopolymer with excellent physicochemical and mechanical properties. Chitin is produced and deposited extracellularly by chitin synthases. Most insects encode two types of chitin synthases, presumably with type A being required for exoskeletons and type B to produce the peritrophic matrix. It is not fully understood, however, which factors contribute to the specificity of each type of chitin synthase. Here we leverage the advantages of Drosophila melanogaster for functional manipulations to evaluate the mechanisms of activity and functional requirements of Kkv (Chitin synthase A) and Chs2 (Chitin synthase B). We first demonstrate that Chs2 is expressed and required in a region in the larval proventriculus that produces the chitin deposited in the peritrophic matrix. We then analyse whether the two chitin synthases can replace each other. We also investigate the subcellular localisation of these chitin synthases in different tissues and their ability to deposit chitin in combination with known auxiliary proteins. Our results indicate that the two different chitin synthases are not functionally equivalent, and that they use specific cellular and molecular mechanisms to deposit chitin. We suggest that the specificity of the different insect chitin synthases may underly the production of chitin polymers with different properties, conferring different physiological activities to the extracellular matrices.

developmental biology↗

bioRxiv2022

Dissecting the roles of Expansion/Rebuf and the chitin synthase Krotzkopf Verkehrt in chitin deposition in Drosophila

Chitin is a highly abundant polymer in nature and a principal component of apical extracellular matrices in insects. In addition, chitin has proved to be an excellent biomaterial with multiple applications. In spite of its importance, the molecular mechanisms of chitin biosynthesis and chitin structural diversity are not fully elucidated yet. To investigate these issues, we use Drosophila as a model. We previously showed that chitin deposition in ectodermal tissues requires the concomitant activities of the chitin synthase enzyme Kkv and the functionally interchangeable proteins Exp and Reb. Here we carry out a cellular and molecular analysis of chitin deposition and we show that chitin polymerisation and chitin translocation to the extracellular space are uncoupled. We find that Kkv activity in chitin translocation, but not in polymerisation, requires the activity of Exp/Reb, and in particular of its conserved N-MH2 domain. The activity of Kkv in chitin polymerisation and translocation correlate with Kkv subcellular localisation, and in absence of Kkv-mediated extracellular chitin deposition, chitin accumulates intracellularly as membrane-less punctae. Furthermore, we find that Kkv and Exp/Reb display a largely complementary pattern at the apical domain, and that Exp/Reb activity regulates the topological distribution of Kkv at the apical membrane. We propose a model in which Exp/Reb regulates the organisation of Kkv complexes at the apical membrane which, in turn, regulates the function of Kkv in extracellular chitin translocation.

developmental biology↗