Biology subjects

Payre, F.

Publications and source records attributed to Payre, F..

7 recordsLinked to original sources

bioRxiv2026

Cancer cachexia overrides sex-specific traits in Drosophila

Cancer cachexia, a metabolic syndrome characterized by pathologic weight loss, dramatically limits therapeutic options and reduces survival. While the mechanisms by which tumors induce wasting of distant organs (particularly muscle and adipose tissues) remain incompletely understood, the influence of biological sex on cachexia progression is even less clear. Here we investigated phenotypic and molecular manifestations of cachexia in both sexes using a model of inducible intestinal tumors in Drosophila. We show that tumor progression leads to the development of severe cachexia both in males and in females manifested by organ atrophies and an inflammatory state. Nevertheless, both phenotypical and molecular cachexic alterations exhibit striking differences between sexes. Transcriptomic analysis show that many genes differentially expressed at high levels in males under normal conditions become downregulated during cachexia, while their expression is upregulated in cachexic females, and reciprocally. Together, sex-specific deregulation in gene expression and metabolic profiles ultimately converge towards a molecular cachexic state that erase or diminish many sex-specific differences otherwise characteristic of healthy males and females. These findings highlight the interplay between oncogenic stress and biological sex in shaping cachexia phenotypes, shedding light on how sex influences the development of cancer cachexia.

developmental biology↗

bioRxiv2025

3D dynamics of trans enhancer-promoter interactions in living Drosophila embryos reveals spatiotemporal thresholds for transcription activation

While it is well acknowledged that specific enhancer-promoter interactions are essential for transcription, the spatiotemporal thresholds required for transcription initiation remain unclear. Here, we employed the phenomenon of transvection, where an enhancer activates the target gene in trans at the homologous position, to analyze the mechanism of long-range enhancer-promoter interactions. We combined the MS2- and PP7-based RNA labeling with the ParB/parS DNA labeling to simultaneously visualize active transcription and a target DNA locus in living Drosophila embryos. By quantifying the 3D enhancer-promoter distances in nuclei that exhibited active or inactive transcription, we found that sustained proximity between the enhancer and promoter is necessary and sufficient to initiate transcription. The enhancer-promoter proximity was established before transcription initiation and remained stable after the termination, suggesting the localization of an enhancer and the target promoters in a "transcription hub." When transvection occurred, the cis-linked reporter gene showed a delayed activation and reduced mRNA production, suggesting homologous promoter competition in the hub. Our DNA-labeled co-transvection assay sheds insights into the activation criteria for the long-range enhancer-promoter interactions and provides a stepping stone for future endeavors to understand the complex gene regulation in 3D space.

developmental biology↗

bioRxiv2023

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in legs, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis and pri was known to control leg development through misunderstood mechanisms, we investigated the role of Ubr3 in mediating pri function in legs. We found that pri play several roles during leg development both in patterning and in cell survival. At larval pupal transition, Pri peptides cooperate with Ubr3 to insure cell survival and leg morphogenesis. Earlier, during larval stage, pri activates independently of Ubr3 tarsal transcriptional programs and Notch and EGFR signalling pathways. Our results highlight Ubr3 dependent and independent functions of Pri peptides and their pleiotropy. Moreover, we reveal that the smORF peptide family is a reservoir of overlooked developmental regulators, displaying distinct molecular functions and orchestrating leg development. Summary statementPri smORF peptides activate multiple actors regulating signalling pathways, transcription and apoptosis by distinct mechanisms to insure tarsal patterning and epithelial morphogenesis during leg development.

developmental biology↗

bioRxiv2023

Crosstalk between chromatin and the transcription factor Shavenbaby defines transcriptional output along the Drosophila intestinal stem cell lineage.

The transcription factor Shavenbaby (Svb), the only member of the OvoL family in Drosophila, controls intestinal stem cell differentiation. Post-translational modification of Svb produces two protein isoforms, Svb-ACT and Svb-REP, which promote intestinal stem cell renewal or differentiation, respectively. Using engineered cell lines, we express either isoform to define their mode of action, and develop an unbiased method to identify Svb target genes in intestinal cells. Within a given cell type, Svb-ACT and Svb-REP antagonistically regulate the expression of a set of target genes, binding specific enhancers whose accessibility is constrained by. During intestinal differentiation, the set of target genes progressively changes, together with chromatin accessibility. Moreover, Svb-REP binding stabilizes three-dimensional enhancer-promoter loops, while influencing the local chromatin landscape to repress target genes. We propose that SvbACT-to-REP switch promotes enterocyte differentiation of intestinal stem cells through direct gene regulation and chromatin remodeling.

genomics↗

bioRxiv2019

Shavenbaby protein isoforms orchestrate the self-renewal versus differentiation of Drosophila intestinal stem cells

Signaling pathways are key regulators of adult stem cell homeostasis and underlying mechanisms are often deregulated in cancers. Recent studies of epithelial tumors have involved OvoL/Svb transcription factors, which produce isoforms with antagonistic activities. Here we show that Svb, the unique OvoL factor in Drosophila, directly integrates multiple signaling inputs to coordinate the behavior of adult intestinal stem cell lineage. Under steady state, Svb mediates Wnt and EGFR signaling to ensure stem cell renewal and progenitor survival. This requires the post-translational processing of Svb into a transcriptional activator by Polished rice (Pri) regulatory peptides, under the regulation of ecdysone signaling. In response to PDM1, Svb expression is specifically maintained in enterocytes where it acts as a transcriptional repressor sufficient to override mitogenic signals and impose differentiation. Altogether, these results demonstrate that the OvoL/Svb transcriptional switch controls the balance between stem cell survival, self-renewal and differentiation.

developmental biology↗

bioRxiv2018

millepattes micropeptides are an ancient developmental switch required for embryonic patterning

Small open reading frames (smORFs) that code for \"micropeptides\" (10-100 amino acids) exhibit remarkable evolutionary complexity. Conserved micropeptides encoded by the millepattes (mlpt) gene are essential in Tribolium for embryogenesis but in Drosophila, function only in leg and cuticle differentiation. We find that a module identified in Drosophila trichome patterning, comprising Mlpt, UBR3, and Shaven-baby (Svb), coordinates early embryo patterning in several insect orders. Intriguingly, Mlpt segmentation function can be re-awakened in the Drosophila blastoderm, demonstrating the potency of an ancestral developmental switch retained despite evolving embryonic patterning modes. smORFs like millepattes thus illustrate plasticity of micropeptide functions despite constraints of essential genetic networks.\n\nOne sentence summaryA module comprising the small ORFs mlpt/pri/tal, the transcription factor Svb, and the ubiquitin ligase UBR3, possesses an ancestral function in insect embryo patterning which is lost in flies but reactivated when Svb expression is restored.

developmental biology↗

bioRxiv2017

Shavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis

To compensate for accumulating damages and cell death, adult homeostasis (e.g., body fluids and secretion) requires organ regeneration, operated by long-lived stem cells. How stem cells can survive throughout the animal life yet remains poorly understood. Here we show that the transcription factor Shavenbaby (Svb, OvoL in vertebrates) is expressed in renal/nephric stem cells (RNSCs) of Drosophila and required for their maintenance during adulthood. As recently shown in embryos, Svb function in adult RNSCs further needs a post-translational processing mediated by Polished rice (Pri) smORF peptides and impairing Svb function leads to RNSC apoptosis. We show that Svb interacts both genetically and physically with Yorkie (YAP/TAZ in vertebrates), a nuclear effector of the Hippo pathway, to activate the expression of the inhibitor of apoptosis DIAP1. These data therefore identify Svb as a novel nuclear effector in the Hippo pathway, critical for the survival of adult somatic stem cells.

developmental biology↗