Biology subjects

Gaugue, I.

Publications and source records attributed to Gaugue, I..

7 recordsLinked to original sources

bioRxiv2026

Xrp1 integrates cellular stress through different control modes in Drosophila

Cells and tissues have the ability to respond to different stresses and maintain their homeostasis. The b-Zip transcription factor Xrp1 was found to play a pivotal role in this context in Drosophila. Xrp1 is required for the response to irradiation, in genetic conditions of ribosomal protein (Rp) deficiency leading to cell competition, and more generally in mediating the Integrated Stress Response (ISR). However, how these diverse stresses converge to and activate Xrp1 is still unclear. Our results demonstrate the existence of three separate mechanisms of Xrp1 induction. In response to Rp stress, a short isoform of Xrp1 is produced and requires the function of the ribosomal protein RpS12. In response to irradiation, a specific mRNA isoform is transcriptionally induced, which encodes the Xrp1-short protein isoform, in a p53-dependent manner. In response to the ISR, the long isoform of Xrp1 is translated by the derepression of a uORF present on the Xrp1 5'UTR, a mechanism that requires eIF2 phosphorylation, RpS12, and a transcriptional induction by ATF4. Therefore, our work provides a comprehensive understanding of the role of Xrp1 in different situations of cellular stress, illustrating the complex level of integration of the mechanisms controlling this central gene.

developmental biology↗

bioRxiv2026

Tissue mechanics sets developmental scaling of collective cell migration

Despite substantial variation in adult size, animals within a species maintain consistent tissue patterns and shapes, a core property known as developmental scaling or size invariance. Developmental scaling has predominantly been attributed to the scaling of morphogen gradients and gene patterns to maintain positional information and cell fate specification1,2. However, development also necessitates collective cell flows that reshape tissues and reposition cells3,4. How these flows adapt to body size remains unclear. By combining quantitative live imaging, experimental perturbations, and physical modeling in the Drosophila thorax epithelium, we address this question in the context of a fundamental process: collective cell migration. We find that migration velocity scales linearly with tissue size, accounting for size-invariant cell positioning. While gene patterning scales with tissue size and modulates force generation, it is not sufficient to ensure proper velocity scaling. Instead, tissue mechanical properties govern the dependence of migration velocity on tissue size, enabling developmental scaling within the physiological range of animal sizes. These findings uncover principles and limits of size invariance by revealing how tissue mechanics sets the scaling behavior of collective cell flows with organismal size.

developmental biology↗

bioRxiv2026

Morphodynamic domains enable integration of live morphometrics and spatial transcriptomics

Tissue development emerges from the coordinated behaviors of thousands of cells, orchestrated by gene regulatory networks. Recent methodological advances now enable high-resolution live imaging of cell- and tissue-scale dynamics and the construction of spatially resolved gene expression atlases. However, quantitatively linking these modalities remains a central challenge, limiting our ability to understand how gene regulatory networks drive cell- and tissue-scale behaviors. Here, using the Drosophila thorax epithelium as a model system, we introduce an analytical and computational framework based on tissue morphodynamic domains: regions defined by coherent cell and tissue dynamics extracted from live imaging morphometrics. Integrating morphodynamic domains with spatial transcriptomics enables the inference of gene regulatory networks associated with distinct spatial cell- and tissue-level behaviors. Statistical cross-scale analyses further allow the interrogation and validation of gene function, confirming or revealing regulators of specific morphogenetic dynamics. In particular, our framework uncovers a role for the Toll-like receptor Tollo in modulating tissue flow, contraction, and apoptosis. Together, our work establishes a framework that integrates spatial transcriptomics with quantitative, multiscale live morphometrics, providing a generalizable strategy to probe and understand developmental processes.

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↗

bioRxiv2022

Systematic characterization of Drosophila RhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division.

Cell proliferation is central to epithelial tissue development, repair and homeostasis. During cell division, small RhoGTPases control both actomyosin dynamics and cell-cell junction remodelling to faithfully segregate the duplicated genome while maintaining tissue polarity and integrity. To decipher the mechanisms of RhoGTPases spatiotemporal regulation during epithelial cell division, we generated a transgenic fluorescently tagged library for Drosophila Rho Guanine exchange factors (GEF) and GTPase activating proteins (GAP), and systematically characterized their endogenous distributions by time- lapse microscopy. Thereby, we unveiled candidate regulators of the interplay between actomyosin and junctional dynamics during epithelial cell division. Building on these findings, we uncovered that during cytokinesis, Cysts and RhoGEF4 play sequential roles in mechanosensing and de novo junction formation, respectively. We foresee that the RhoGEF/GAP library will be a key resource to understand the broad range of biological processes regulated by RhoGTPases.

developmental biology↗

bioRxiv2022

Homeotic compartment curvature and tension control spatiotemporal folding dynamics.

Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.

developmental biology↗

bioRxiv2021

Pre-meiotic pairing of homologous chromosomes during Drosophila male meiosis

In the early stages of meiosis, maternal and paternal chromosomes pair with their homologous partner and recombine to ensure exchange of genetic information and proper segregation. These events can vary drastically between species and between males and females of the same species. In Drosophila, in contrast to females, males do not form synaptonemal complexes (SCs), do not recombine and have no crossing-over; yet, males are able to segregate their chromosomes properly. Here, we investigated the early steps of homologues pairing in Drosophila males. We found that homologues are not paired in germline stem cells (GSCs) and become paired in the mitotic region before meiotic entry, similarly to females. Surprisingly, male germline cells express SC proteins, which localize to centromeres and promote pairing. We further found that the SUN/KASH (LINC) complex and microtubules are required for homologues pairing as in females. Chromosome movements are however much slower than in females and we demonstrate that this slow dynamic is compensated in males by having longer cell cycles. In agreement, slowing down cell cycles was sufficient to rescue pairing-defective mutants in female meiosis. Our results demonstrate that although meiosis differs significantly between males and females, sex-specific cell cycle kinetics are integrated with similar molecular mechanisms to achieve proper homologues pairing.

developmental biology↗