Biology subjects

Poidevin, M.

Publications and source records attributed to Poidevin, M..

9 recordsLinked to original sources

bioRxiv2025

Drosophila Sociality Influences Immune Peptide Load and Apoptosis-induced Tumor Suppression independently of the Antitumor Peptide Defensin

Patients social environment might influence cancer outcome. This potentially happens in Drosophila, as we previously reported that the social context influences the growth of intestinal tumors. To uncover the underlying social-induced physiological mechanisms, we performed RNA-seq of isogenized beheaded tumorous Drosophila. Importantly, expression of several immune peptides varied according to the social-induced tumor growth effect. Furthermore, ectopic expression in tumors of the apoptotic-inhibitor p35 suppressed the social-induced effect. Next, we challenged the immune peptide Defensin, previously reported to suppress imaginal disc tumor growth through a cell-death/JNK-dependent network. Nonetheless, the social-induced tumor suppression was maintained upon Defensin overexpression or JNKK-knockdown in tumors, and in defensin mutants. Surprisingly, tumor growth was reduced in the latter, indicating that Defensin sustains the growth of these intestinal tumors. In summary, our study indicates that the social context affects the immune response and that a given immune peptide may have opposite effects depending on tumor type.

cancer biology↗

bioRxiv2025

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

Drosophila immunity has been the focus of intense study and has impacted other research fields including innate immunity and agriculturally or epidemiologically relevant investigations of insect pests and vectors. Unsurprisingly for such a large body of work, some published results were later found to be irreplicable. Although some results have been contradicted in the literature, many have no published follow-up, either due to a lack of research or low motivation to publish negative or contradictory results. We have addressed this by performing a reproducibility project that analyses the conceptual replicability of claims from articles published on Drosophila immunity before 2011. To assess replicability, we extracted claims from 400 articles on the Drosophila immune response to bacteria and fungi and performed preliminary verification by comparing these claims to other published literature in the field. Using alternative approaches, we also experimentally tested some unchallenged claims, with no published follow-up. The intent of this analysis was to centralize evidence on insights and findings to improve clarity for scientists that may base research programs on these data. Although the aim of the ReproSci project is to assess the replicability of claims made in articles published in the field of Drosophila immunity, it is in no way an assessment of the scientific value of the research. All our data are published on a publicly available website associated with this article (https://ReproSci.epfl.ch/) that encourages community participation. This article provides a short summary of claims that were found to have contradictory evidence, which may help the community to assess past findings on Drosophila immunity and improve clarity going forward. Statistical analysis of this reproducibility study and metascience insights obtained from this approach are discussed in a companion article.

genetics↗

bioRxiv2025

The secreted Nimrod NimB1 negatively regulates early steps of apoptotic cell phagocytosis in Drosophila

Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1 null mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.

immunology↗

bioRxiv2025

An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility

Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms involving an RNA intermediate, occupy large portions of all eukaryotic genomes. A great majority of their manifold copies remain silenced in somatic cells, nevertheless, some are transcribed, often in a tissue specific manner, and a small fraction retains its ability to mobilize. Retrotransposon expression or mobility are increasingly recognized to contribute to normal development and tissue homeostasis, as well as to aging and disease. While it is well characterized that retrotransposon sequences may provide cis regulatory elements for neighboring genes, how their own expression and mobility are achieved in different somatic contexts is not well understood. Here, using long-read DNA sequencing, we characterize somatic retrotransposition in the Drosophila intestine. We show that retroelement mobility does not change significantly upon aging and is limited to very few active sub-families of retrotransposons. Importantly, we identify a polymorphic donor locus of an endogenous LTR retroviral element rover, active in the intestinal tissue. We reveal that gut activity of the rover donor copy depends on its genomic environment. Without affecting local gene expression, the copy co-opts its upstream enhancer sequence, rich in transcription factor binding sites, for somatic expression. Further we show that escargot, a snail-type transcription factor critical for gut progenitor cell function, can drive transcriptional activity of the active rover copy. These data provide new insights into how locus-specific features allow active retrotransposons to produce functional transcripts and mobilize in a somatic lineage.

genomics↗

bioRxiv2021

A Fatty Acid Anabolic Pathway in Specialized-Cells Remotely Controls Oocyte Activation in Drosophila

Pheromone-mediated partner recognition is crucial for maintenance of animal species. Here, we discover a metabolic link between pheromone and gamete physiology. In female genital tract, oocyte maturation is arrested at a specific meiotic-phase. Release of this arrest, called oocyte-activation, is triggered by a species-dependent signal. We show in Drosophila melanogaster that oenocytes, which produce the fatty acids (FAs) used as precursors of cuticular hydrocarbons (CHCs), including pheromones, are also essential for oocyte activation. We identified a set of FA-anabolic enzymes required within oenocytes for the synthesis of a particular FA that is not a CHC precursor but controls oocyte activation. Our study thus reveals that two tightly linked FA-anabolic pathways act in parallel, one to produce sexual pheromones, the other to initiate embryonic development. Given that pheromone-deficient Drosophila melanogaster females are highly attractive for males irrespective of their species, this oenocyte function might have evolved to prevent hybrid development.

physiology↗

bioRxiv2019

Hemocyte-targeted gene expression in the female malaria mosquito using the hemolectin promoter from Drosophila

Hemocytes, the immune cells in mosquitoes, participate in immune defenses against pathogens including malaria parasites. Mosquito hemocytes can also be infected by arthropod-borne viruses but the pro- or anti-viral nature of this interaction is unknown. Although there has been progress on hemocyte characterization during pathogen infections in mosquitoes, the specific contribution of hemocytes to immune responses and the hemocyte-specific functions of immune genes and pathways remain unresolved due to the lack of genetic tools to manipulate gene expression in these cells specifically. Here, we used the Gal4-UAS system to characterize the activity of the Drosophila hemocyte-specific hemolectin promoter in the adults of Anopheles gambiae, the malaria mosquito. We established an hml-Gal4 driver line that we further crossed to a fluorescent UAS responder line, and examined the expression pattern in the adult progeny driven by the hml promoter. We show that the hml regulatory region drives hemocyte-specific transgene expression in a subset of hemocytes, and that transgene expression is triggered after a blood meal. The hml promoter drives transgene expression in differentiating prohemocytes as well as in differentiated granulocytes. Analysis of different immune markers in hemocytes in which the hml promoter drives transgene expression revealed that this regulatory region could be used to study phagocytosis as well as melanization. Finally, the hml promoter drives transgene expression in hemocytes in which onyongnyong virus replicates. Altogether, the hml promoter constitutes a good tool to drive transgene expression in hemocyte only and to analyze the function of these cells and the genes they express during pathogen infection in Anopheles gambiae.

genetics↗

bioRxiv2019

Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.\n\nAuthor summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.\n\nInterestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

immunology↗

bioRxiv2019

Differential Metabolic Sensitivity of mTORC1- and mTORC2-Dependent Overgrowth

The glycolytic/lipogenic axis promotes the synthesis of energetic molecules and building blocks necessary to support cell growth, although the absolute requirement of this metabolic axis must be deeply investigated. Here, we used Drosophila genetics and focus on the mTOR signaling network that controls cell growth and homeostasis. mTOR is present in two distinct complexes, mTORC1 and mTORC2. The former directly responds to amino acids and energetic levels, whereas the latter is required to sustain the signaling response downstream of insulin-like-peptide (Ilp) stimulation. Either signaling branch can be independently modulated in most Drosophila tissues. We confirm this independency in the fat tissue. We show that ubiquitous over-activation of mTORC1 or Ilp signaling affects carbohydrate and lipid metabolism, supporting the use of Drosophila as a powerful model to study the link between growth and metabolism. We show that cell-autonomous restriction of glycolysis or lipogenesis in fat cells impedes overgrowth dependent on Ilp-but not mTORC1-signaling. Additionally, ubiquitous deficiency of lipogenesis (FASN mutants) results in a drop in mTORC1 but not Ilp signaling, whereas, at the cell-autonomous level, lipogenesis deficiency affects none of these signals in fat cells. These findings thus, reveal differential metabolic sensitivity of mTORC1- and Ilp-dependent overgrowth. Furthermore, they suggest that local metabolic defects may elicit compensatory pathways between neighboring cells, whereas enzyme knockdown in the whole organism results in animal death. Importantly, our study weakens the use of single inhibitors to fight mTOR-related diseases and strengthens the use of drug combination and selective tissue-targeting.

cell biology↗

bioRxiv2018

Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilised CRISPR gene editing to delete all known immune inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, acting either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

immunology↗