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Current papers in developmental biology and gene function
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What's hot today
November 2025 September 2025 August 2025 July 2025 June2025 June2025 May 2025 April 2025 March 2025 February 2025 January 2025 December 2024 November 2024 October 2024 September 2024 August 2024 July 2024 June 2024 May 2024 April 2024 March 2024 February 2024 January 2024 December 2023 November 2023 October 2023 December 2022 December 2021 December 2020 December 2019 December 2018 | Tatar, M., Zheng, W., Yadav, S., Yamamoto, R., Curtis-Joseph, N., Li, S., Wang, L., Parkhitko, A. A. (2025). An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan. PLoS Genet, 21(6):e1011640 PubMed ID: 40523036
Summary: Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, a series of Drosophila insulin-like receptor (dInr) mutants was developed with single amino acid substitutions that extend lifespan but differentially affect insulin sensitivity, growth and reproduction. Transheterozygotes of canonical dInr mutants (Type I) extend longevity and are insulin-resistant, small and weakly fecund. In contrast, a dominant mutation (dInr353, Type II) within the Kinase Insert Domain (KID) robustly extends longevity but is insulin-sensitive, full-sized, and highly fecund. Transcriptome and metabolome analyses were applied to explore how dInr353 slows aging without insulin resistance. Type I and II mutants overlap in many pathways but also produce distinct transcriptomic profiles that include differences in innate immune and reproductive functions. In metabolomic analyses, the KID mutant dInr353 reprograms methionine metabolism in a way that phenocopies dietary methionine restriction, in contrast to canonical mutants which are characterized by upregulation of the transsulfuration pathway. Because abrogation of S-adenosylhomocysteine hydrolase blocks the longevity benefit conferred by dInr353, its is concluded that the methionine cycle reprogramming of Type II is sufficient to slow aging. Metabolomic analysis further revealed the Type II mutant is metabolically flexible: unlike aged wildtype, aged dInr353 adults can reroute methionine toward the transsulfuration pathway, while Type I mutant flies upregulate the transsulfuration pathway continuously from young age. Altered insulin/insulin growth factor signaling has the potential to slow aging without the complications of insulin resistance by modulating methionine cycle dynamics. | Yoshino, J., Chiu, A., Morita, T., Yin, C., Tenedini, F. M., Sokabe, T., Emoto, K., Parrish, J. Z. (2025). Heat-off responses of epidermal cells sensitize Drosophila larvae to noxious inputs. bioRxiv, PubMed ID: 40501750
Summary: Perception of external thermal stimuli is critical to animal survival, and although an animal's skin is the largest contact surface for thermal inputs, contributions of skin cells to noxious temperature sensing have not been extensively explored. This study showed that exposure to heat transiently sensitizes Drosophila larvae to subsequent noxious stimuli. This sensitization is induced by prior stimulation of epidermal cells but not nociceptors, suggesting that epidermal cells modulate nociceptor function in response to heat exposure. Indeed, Drosophila epidermal cells are intrinsically thermosensitive, exhibiting robust heat-off responses following warming to noxious temperatures as well as responses to cooling below comfortable temperatures. Further, epidermal heat-off calcium responses involve influx of extracellular calcium and require the store-operated calcium channel Orai<.a> and its activator Stim. Finally, epidermal heat-off responses and heat-evoked nociceptive sensitization exhibit similar temperature dependencies, and Stim and Orai were found to be required in epidermal cells for heat-evoked nociceptive sensitization. Hence, epidermal thermosensory responses provide a form of adaptive sensitization to facilitate noxious heat avoidance. |
| Kashio, S., Miura, M. (2025). S-adenosylmethionine metabolism buffering is regulated by a decrease in glycine N-methyltransferase via the nuclear ubiquitin-proteasome system. Proc Natl Acad Sci U S A, 122(26):e2417821122 PubMed ID: 40553497
Summary: Metabolic homeostasis is essential for survival; however, many studies have focused on the fluctuations of these factors. Furthermore, while metabolic homeostasis depends on the balance between the production and consumption of metabolites, there have been limited investigations into the mechanisms regulating their consumption. S-adenosylmethionine (SAM) metabolism has diverse functions, including methylation, polyamine biosynthesis, and transsulfuration, making its regulation and control crucial. Recent studies have revealed the feedback regulation of SAM production; however, the mechanisms governing its consumption are still poorly understood. This study focused on the stability of SAM levels in the fat body (FB) of Drosophila, which serves as a functional equivalent of the mammalian liver and adipose tissue, under conditions of SAM shortage, including nutrient deprivation. This study found that glycine N-methyltransferase (Gnmt), a major SAM-consuming methyltransferase in the FB, decreased via the nuclear ubiquitin-proteasome system (UPS), along with the inhibition of SAM synthesis and starvation. The inhibition of Gnmt level reduction by suppression of the nuclear UPS causes starvation tolerance. Thus, the regulation of Gnmt levels through nuclear UPS-mediated reduction helps maintain SAM levels under SAM shortage conditions. | Jin, L., Kim, C. H., Seo, J. T., Moon, S. J. (2025). . Dietary salt induces taste desensitization via receptor internalization in Drosophila in a sexually dimorphic manner. Mol Cells, 48(8):100242 PubMed ID: 40541634
Summary: Sodium homeostasis, which is critical for survival, includes mechanisms for regulating salt intake that integrate central neural pathways with the peripheral taste system. Although the central homeostatic mechanisms of salt appetite are well-studied, the mechanisms by which dietary salt modulates peripheral taste responses remain unclear. Increased dietary salt reduces salt preference in Drosophila by desensitizing sweet gustatory receptor neurons independent of internal sodium levels. A reversible suppression of salt-evoked neural responses following salt exposure accomplished via clathrin-mediated endocytosis in males and both clathrin- and C-terminal binding protein-dependent endocytosis in females. Reversing gustatory receptor neuron sexual identity switched the desensitization pattern, indicating cell-autonomous control of this sexual dimorphism. Moreover, C-terminal binding protein-mediated macropinocytosis in females also dampened sweet taste responses, revealing a sex- and modality-specific mechanism underlying sensory adaptation. These findings reveal dietary experience can affect feeding behavior by reprograming peripheral taste responses, clarifying the plasticity of nutrient sensing. |
| Millington, J. W., Lopez, J. A., Sajjadian, A. M., Scheffler, R. J., DeFelice, B. C., Ludington, W. B., Good, B. H., O'Brien, L. E., Huang, K. C. (2025). Gut microbe-derived lactic acid optimizes host energy metabolism during starvation. bioRxiv, PubMed ID: 40502158
Summary: Gut microbes convert dietary compounds into an array of metabolites that can directly provide energy to their host and indirectly impact host metabolism as systemic endocrine signals.This study shows that gut microbe-derived metabolites can extend Drosophila melanogaster survival during starvation, despite minimal alteration of dietary energy intake. Combining survival assays with mathematical modeling and untargeted metabolomics, a single, dominant mediator of starvation resilience was identified: lactic acid produced by the commensal bacterium Lactiplantibacillus plantarum. The basis of starvation resilience is not catabolism of lactic acid using lactate dehydrogenase, but rather increased dietary energy yield through lactic acid-driven promotion of oxidative phosphorylation. These findings emphasize the role of the microbiome as a source of endocrine cues coordinating host metabolism and underscore the potential of microbiome-derived metabolites as therapeutic molecules for manipulating metabolic health and preventing disease. | Geronazzo, J., Heimerl, A., Lindell, L., McCrimmon, S., Stormer, C., Horvai, B., Johnson, I. P., Peterson, T. M., Zuckerman, J., Scott, A. I., Course, M. M. (2025). Characterizing fatty acid oxidation genes in Drosophila. G3 (Bethesda), PubMed ID: 40519079
Summary: This study leveraged the power and tractability of Drosophila genetics to better understand the molecular mechanisms underlying a group of rare genetic diseases known as fatty acid oxidation disorders. CRISPR-Cas9 was used to generate mutations in six putative fatty acid oxidation genes in Drosophila, then analyze the phenotypes and acylcarnitine profiles of these flies. While Arc42 and CG4860 are both predicted orthologs of human ACADS, only Arc42 loss of function mirrors the acylcarnitine profile of ACADS loss of function. Acylcarnitine profiles also support a previous identification of Mcad as the likely ACADM ortholog, and reveal the deleterious effects of a single codon deletion in Mtp&alpha: (the predicted human HADHA ortholog). Finally, it was observed that loss of function in Etf-QO and in CG7834-predicted orthologs of human ETFDH and ETFB, respectively-is homozygous lethal in flies. Producing animal models like these will enable new approaches to studying fatty acid oxidation disease progression, symptomatic variability, and therapeutic intervention. |
Tuesday October 28th - Adult Neural Development, Structure and Function |
| Ainsworth, J., Zhao, Y., Gao, K., Gravina, N. M., Goldberg, Z. H., Pinkerton, C., Rifkin, S. A., Ernst, A. M., Garcia, H. G., Perry, M. W. (2025). Cell fate ratios are encoded by transcriptional dynamics in the Drosophila retina. Curr Biol, 35(12):2946-2959.e2945 PubMed ID: 40499552
Summary: Although transcription happens in bursts, it is unclear whether variation in the rate and pattern of bursting matters during animal development. We examined whether the amount and timing of transcription influence the ratio of cell types produced during stochastic patterning of the Drosophila retina. This system is balanced between 2 outcomes: ∼70% of R7 photoreceptors (PRs) express Rhodopsin 4 (Rh4), and the rest express Rhodopsin 3 (Rh3). Cell fate depends on the cell-intrinsic binary decision to express the transcription factor Spineless (Ss). Changing the ss bursting pattern by replacing the ss core promoter led to a different ratio of R7 PR types. It was hypothesized that random variation in the timing of transcriptional initiation followed by autoregulation might control the outcome. Instead, this study found that the decision occurs before R7 specification and before protein is made, with no feedback via Ss protein. Surprisingly, this happens in a field of progenitor cells that give rise to all retina cell types, which all initially transcribe ss. A subset stops transcribing ss over time. Those that become R7s and maintain ss transcription take the Ss-ON/Rh4 fate. Live imaging of ss transcription suggests increased time spent in off periods could decrease the probability of new transcription and therefore the Ss-ON ratio. Transiently increasing continuity of transcription produces all Ss-ON outcomes, while introducing longer gaps lowers the ratio. Targeting CBP to the ss locus increases the ratio, indicating a repressive role for chromatin state during periods when transcription is inactive. It is concluded that ratio is set by the amount and dynamics of ss transcription. | Sun, Y., Duan, Y., Gao, P., Liu, C., Jin, K., Dou, S., Tang, W., Zhang, H., Lu, J. (2025). Upstream open reading frames buffer translational variability during Drosophila evolution and development. Elife, 14 PubMed ID: 40478227
Summary: Protein abundance tends to be more evolutionarily conserved than mRNA levels both within and between species, yet the mechanisms underlying this phenomenon remain largely unknown. Upstream open reading frames (uORFs) are widespread cis-regulatory elements in eukaryotic genomes that regulate translation, but it remains unclear whether and how uORFs contribute to stabilizing protein levels. In this study, ribosome translation simulations on mRNA were performed to quantitatively assess the extent to which uORF translation influences the translational variability of downstream coding sequences (CDSs) across varying contexts. Our simulations revealed that uORF translation dampens CDS translational variability, with buffering capacity increasing in proportion to uORF translation efficiency, length, and number. The translatomes at different developmental stages of two Drosophila species were compared, demonstrating that uORFs buffer mRNA translation fluctuations during both evolution and development. Experimentally, deleting a uORF in the bicoid (bcd) gene-a prominent example of translational buffering-resulted in extensive changes in gene expression and phenotypes in Drosophila melanogaster. Additionally, uORF-mediated buffering was observed between primates and within human populations. Together, these results reveal a novel regulatory mechanism by which uORFs stabilize gene translation during development and across evolutionary time. |
| Hong, M., Hong, J. W. (2025). Promoter strength delimits enhancer threshold in the early Drosophila embryo. Int J Dev Biol, 69(2):81-90 PubMed ID: 40521685
Summary: The enhancer threshold is defined as the minimum concentration of transcription factors (TFs) required to elicit an enhancer response in a given time and space. Here, evidence is presented that the enhancer threshold is relative to promoter strength in the early Drosophila embryo. The apparently inactive even-skipped (eve) minimal stripe element (MSE), in which a single Hunchback (Hb)-binding site is deleted, is functionally complemented by the hsp70 promoter in transgenic embryos. Forced pause release of RNA polymerase II (Pol II) and transcription bubble assays show that both eve and heat shock protein 70 (hsp70) promoters exhibit paused Pol II. However, bioinformatics analyses and transient transfection assays indicate that the strength of the hsp70 promoter is much stronger than that of the eve promoter. Consistently, inactive MSE function is also restored by promoters stronger than the eve promoter. It is conceivable that the functional complementarity between enhancer and promoter strengths defines the enhancer threshold, thus determining whether a genomic locus acts as an enhancer for a particular promoter. | Dima, S. S., Reeves, G. T. (2025). Bulk-level maps of pioneer factor binding dynamics during the Drosophila maternal-to-zygotic transition. Development, 152(13) PubMed ID: 40512118
Summary: Gene regulation by transcription factors (TFs) binding cognate sequences is of paramount importance. For example, the TFs Zelda (Zld) and GAGA factor (GAF) are widely acknowledged for pioneering gene activation during zygotic genome activation (ZGA) in Drosophila. However, quantitative dose/response relationships between bulk TF concentration and DNA binding, an event tied to transcriptional activity, remain elusive. This study mapped these relationships during ZGA: a crucial step in metazoan development. To map the dose/response relationship between nuclear concentration and DNA binding, raster image correlation spectroscopy, a method that can measure biophysical parameters of fluorescent molecules, was use. Although Zld concentration increases during nuclear cycles 10 to 14, its binding in the transcriptionally active regions decreases, consistent with its function as an activator for early genes. In contrast, GAF-DNA binding is nearly linear with its concentration, which sharply increases during the major wave, implicating its involvement in the major wave. This study provides key insights into the properties of the two factors and puts forward a quantitative approach that can be used for other TFs to study transcriptional regulation. |
| Nawar, N., Rits, E., Cohen, L., Wunderlich, Z. (2025). Heterogeneous NF-kappaB activation and enhancer features shape transcription in Drosophila immunity. bioRxiv, PubMed ID: 40475619
Summary: Conserved NF-kappaB signaling pathways shape immune responses in animals. In mammals, NF-kappaB activation patterns and downstream transcription vary with stimulus, cell type, and stochastic differences among identically treated cells. Whether animals without adaptive immunity exhibit similar heterogeneity or rely on distinct immune strategies remains unknown. This study engineered Drosophila melanogaster S2* reporter cells as an immune-responsive model to monitor the dynamics of an NF-kappaB transcription factor, Relish, and downstream transcription in single, living cells. Following immune stimulation, Relish exhibits diverse nuclear localization dynamics that fall into distinct categories, with both the fraction of responsive cells and their activation speed rising with stimulus dose. Pre-stimulus features, including Relish nuclear fraction, predict a cell's responsiveness to stimulation. Simultaneous measurement of Relish and downstream transcription revealed that the probability of transcriptional bursts from immune-responsive enhancers correlates with Relish nuclear fraction. The number of NF-kappaB binding sites tunes transcriptional activity among immune enhancers. This study uncovers heterogeneity in NF-kappaB activation and target gene expression within Drosophila, illustrating how dynamic NF-kappaB behavior and enhancer architecture tune gene regulation. | Simonov, R. A., Olenkina, O. M., Nenasheva, V. V., Abramov, Y. A., Lavrov, S. A., Fedotova, A. A., Shevelyov, Y. Y. (2025). Binding of Transcriptional Activator to Silent Loci Causes Their Detachment from the Nuclear Lamina in Drosophila Neurons and Salivary Gland Cells. Int J Mol Sci, 26(12) PubMed ID: 40565256
Summary: In mammals, the binding of transcriptional activators leads to the repositioning of silent loci from the nuclear periphery to the nuclear interior. However, it remained unknown whether the same mechanism functions in Drosophila. Using FISH and DamID, this study has shown that binding the GAL4 activator to the silent loci causes weakening of their interactions with the nuclear lamina and relocalization inside nuclei in Drosophila salivary gland cells and neurons. This mimics the removal from the nuclear periphery of a neuron-specific gene upon its activation in neurons. Salivary gland cells contain polytene chromosomes with mechanical properties, different from chromosomes of diploid cells, while neurons represent predominantly non-dividing cell type. The results indicate a causal relationship between transcriptional activator binding and changes in the intranuclear position of loci in Drosophila. They also point to the similarity in general chromatin dynamics in mammals and Drosophila, thus strengthening the role of model organisms in studying genome architecture. |
Friday October 24th - Cytoskeleton |
| Lince-Faria, M., Ferreira-Silva, A., Pimenta-Marques, A. (2025). The Centriole Stability Assay: A Method to Investigate Mechanisms Involved in the Maintenance of the Centrosome Structure in Drosophila Cultured Cells. Bio Protoc, 15(11):e5330 PubMed ID: 40511405
Summary: Centrosomes are vital eukaryotic organelles involved in regulating cell adhesion, polarity, mobility, and microtubule (MT) spindle assembly during mitosis. Composed of two centrioles surrounded by the pericentriolar material (PCM), centrosomes serve as the primary microtubule-organizing centers (MTOCs) in proliferating cells. The PCM is crucial for MT nucleation and centriole biogenesis. Centrosome numbers are tightly regulated, typically duplicating once per cell cycle, during the S phase. Deregulation of centrosome components can lead to severe diseases. While traditionally viewed as stable structures, centrosomes can be inactivated or disappear in differentiating cells, such as epithelial cells, muscle cells, neurons, and oocytes. Despite advances in understanding centrosome biogenesis and function, the mechanisms maintaining mature centrosomes or centrioles, as well as the pathways regulating their inactivation or elimination, remain less explored. Studying centrosome maintenance is challenging as it requires the uncoupling of centrosome biogenesis from maintenance. Tools for acute spatial-temporal manipulation are often unavailable, and manipulating multiple components in vivo is complex and time-consuming. This study presents a protocol that decouples centrosome biogenesis from maintenance, allowing the study of critical factors and pathways involved in the maintenance of the integrity of these important cellular structures. | Lenartowski, R., Ostrowski, J., Suwinska, A., Richert, A., Zakrzewski, P., Izdebska, M., Arendt, W., Miller, K. G., Lenartowska, M. (2025). Myosin VI is expressed in developing ovarian follicles in Drosophila but is not essential for effective oogenesis. Front Cell Dev Biol, 13:1535117 PubMed ID: 40530337
Summary: Myosin VI is the only actin-based motor known to move toward the minus end of actin filaments. This protein is involved in many different cellular processes, such as endocytosis, autophagy, secretion, and regulation of actin organization and dynamics. Myosin VI has also been suggested to play an important role in collective migration of border cells and egg chamber development during Drosophila oogenesis. This study shows that myosin VI is expressed in Drosophila germarium as well as in early ovarian follicles, especially in the developing oocyte. As oogenesis progresses, the level of myosin VI in maturing egg chambers decreases, but this protein is present both in the nascent border cell cluster, during its delamination from the epithelium, and then during the early stages of border cell migration. However, myosin VI deficiency in border cells, or even complete lack of this protein in myosin VI mutant do not inhibit border cell migration. Moreover, deficiency/lack of myosin VI does not cause any serious defects in ovarian morphology, egg chamber morphogenesis, oogenesis, and egg development. Thus it is concluded that myosin VI is not a key player in Drosophila oogenesis. |
| Carvalho, C. A., Tame, M. A., St Johnston, D. (2025). Adherens junctions limit septate junction length in Drosophila midgut enterocytes but are not required for polarity. J Cell Sci, 138(13) PubMed ID: 40485276
Summary: Adherens junctions formed by E-cadherin adhesion complexes play central roles in the organisation and apical-basal polarisation of both mammalian and insect epithelia. This study investigated the function of the components of the E-cadherin adhesion complex in the Drosophila midgut epithelium, which establishes polarity by a different mechanism from other fly epithelia and has an inverted junctional arrangement in which the adherens junctions lie below the septate junctions. Unlike other epithelial tissues, loss of E-cadherin, Armadillo (β-catenin) or α-catenin has no effect on the polarity or organisation of the adult midgut epithelium. This is not due to redundancy with other cadherins, as enterocytes lacking E-cadherin, N-cadherin and CadN2 still polarise normally. However, E-cadherin (shg) and armadillo mutants have expanded septate junction domains and shorter lateral domains below the septate junctions, indicating that E-cadherin adhesion complexes limit the basal extent of the septate junctions. Thus, Cadherin-mediated adhesion is dispensable for apical-basal polarity and epithelial organisation in the Drosophila midgut, in contrast to all other epithelia that have been studied so far, but it is required to define the size of the septate junctions and cell height. | Wu, Z., Zhang, Y., Liu, J., Liu, H., Niu, J., Li, Y., Xie, S., Yan, X., Zhu, X., Wei, Q. (2025). Ccdc13 is essential for the assembly of ciliary central microtubules. Natl Sci Rev, 12(6):nwaf095 PubMed ID: 40492112
Summary: Motile cilia are critical for diverse cellular activities, affecting the survival and development of most eukaryotic organisms. Central microtubules (MTs), which are located in the lumen of ciliary axonemes, are non-centrosomal MTs that are crucial for motile cilia beating. However, the formation mechanism of central MTs remains elusive. By using a Drosophila model, this study identified Ccdc13 as a novel regulator for the assembly of central MTs. Ccdc13 localizes along the central MTs and is essential for its formation in sperm flagella, with its deletion consequently affecting the sperm motility and the fertility of male flies. Mechanistically, Ccdc13 directly interacts with Spef1, acting upstream of Spef1 to regulate central MT elongation. Remarkably, the role of Ccdc13 in ciliary central MT formation is conserved in mammals. Ccdc13 deficiency in mice leads to the loss of central MTs in motile ependymal cilia, resulting in abnormal cilia motility and hydrocephalus. Yhese results mark the discovery of Ccdc13 as a novel regulator for ciliary central MT assembly and reveal that the Ccdc13-Spef1 complex is an evolutionarily conserved module that is critical for central MT formation in motile cilia of both flies and mammals. |
| Jensen, C. C., Gurley, N. J., Mathias, A. J., Wolfsberg, L. R., Xiao, Y., Zhou, Z., Bischoff, M. C., Clark, S. E., Slep, K. C., Peifer, M. (2025). A key role of Canoe's intrinsically disordered region in linking cell junctions to the cytoskeleton. J Cell Biol, 224(12) PubMed ID: 41099653
Summary: Adherens junctions regulate tissue architecture, mediating robust yet dynamic cell-cell adhesion and, via cytoskeletal linkage, allowing cells to change shape and move. Adherens junctions contain thousands of molecules linked by multivalent interactions of folded protein domains and intrinsically disordered regions (IDRs). One key challenge is defining mechanisms conferring robust linkage and mechanosensing. Drosophila Canoe and mammalian Afadin provide superb entry points to explore how their complex protein structures and shared IDRs enable function. This study combined genetic, cell biological, and biochemical tools to define how Canoe's IDR functions during morphogenesis. Unlike many of Canoe's folded domains, the proximal IDR is critical for junctional localization, mechanosensing, and function. In its absence, the mutant protein localizes to nuclei. This study took the IDR apart, identifying two conserved stickers that directly bind F-actin, separated by less-conserved spacers. Surprisingly, while mutants lacking the IDR die as embryos with morphogenesis defects, no IDR subregion is essential for viability. Instead, stickers and spacers act combinatorially to ensure localization, mechanosensing, and function. | Hardin, K. R., Penas, A. B., Joubert, S., Ye, C., Myers, K. R., Zheng, J. Q. (2025). A critical role for the fascin family of actin bundling proteins in axon development, brain wiring and function. Mol Cell Neurosci, 134:104027 PubMed ID: 40553926
Summary: Actin-based cell motility drives many neurodevelopmental events including guided axonal growth. Fascin is a major family of F-actin bundling proteins, but its role in axon development in vivo and brain wiring remains unclear. Here, we report that fascin is required for axon development, brain wiring and function. We show that fascin is enriched in the motile filopodia of axonal growth cones and its inhibition impairs axonal extension and branching of hippocampal neurons in culture. We next provide evidence that fascin is essential for axon development and brain wiring in vivo using Drosophila melanogaster as a model. Drosophila expresses a single ortholog of mammalian fascin called Singed (Sn), which is expressed in the mushroom body (MB) of the central nervous system. Loss of SN causes severe MB disruption, marked by α- and β-lobe defects indicative of altered axonal guidance. SN-null flies also exhibit defective sensorimotor behaviors as assessed by the negative geotaxis assay. MB-specific expression of SN in SN-null flies rescues MB structure and sensorimotor deficits, indicating that SN functions autonomously in MB neurons. Together, these data from primary neuronal culture and in vivo models highlight a critical role for fascin in brain development and function. |
Thursday October 23st - Embryonic Development |
| Gomez, J. M., Nolte, H., Vogelsang, E., Dey, B., Takeda, M., Giudice, G., Faxel, M., Haunold, T., Cepraga, A., Zinzen, R. P., Kruger, M., Petsalaki, E., Wang, Y. C., Leptin, M. (2024). Differential regulation of the proteome and phosphosproteome along the dorso-ventral axis of the early Drosophila embryo. Elife, 13 PubMed ID: 39221782
Summary: The initially homogeneous epithelium of the early Drosophila embryo differentiates into regional subpopulations with different behaviours and physical properties that are needed for morphogenesis. The factors at top of the genetic hierarchy that control these behaviours are known, but many of their targets are not. To understand how proteins work together to mediate differential cellular activities, the proteomes and phosphoproteomes of the three main cell populations along the dorso-ventral axis was studied in an unbiased manner during gastrulation using mutant embryos that represent the different populations. 6111 protein groups and 6259 phosphosites were detected of which 3398 and 3433 respectively, were differentially regulated. The changes in phosphosite abundance did not correlate with changes in host protein abundance, showing phosphorylation to be a regulatory step during gastrulation. Hierarchical clustering of protein groups and phosphosites identified clusters that contain known fate determinants such as Doc1, Sog, Snail and Twist. The recovery of the appropriate known marker proteins in each of the different mutants validated the approach, but also revealed that two mutations that both interfere with the dorsal fate pathway, Toll10B and serpin27aex do this in very different manners. Diffused network analyses within each cluster point to microtubule components as one of the main groups of regulated proteins. Functional studies on the role of microtubules provide the proof of principle that microtubules have different functions in different domains along the DV axis of the embryo. | Trujillo, E. M., Lee, S. R., Aguayo, A., Torosian, T. C., Cripps, R. M. (2024). Enhanced expression of the myogenic factor Myocyte enhancer factor-2 in imaginal disc myoblasts activates a partial, but incomplete, muscle development program. Dev Biol, 516:82-95 PubMed ID: 39111615
Summary: The Myocyte enhancer factor-2 (MEF2) transcription factor plays a vital role in orchestrating muscle differentiation. While MEF2 cannot effectively induce myogenesis in naive cells, it can potently accelerate myogenesis in mesodermal cells. This includes in Drosophila melanogaster imaginal disc myoblasts, where triggering premature muscle gene expression in these adult muscle progenitors has become a paradigm for understanding the regulation of the myogenic program. This study investigated the global consequences of MEF2 overexpression in the imaginal wing disc myoblasts, by combining RNA-sequencing with RT-qPCR and immunofluorescence. The formation of sarcomere-like structures was observed that contained both muscle and cytoplasmic myosin, and significant upregulation of muscle gene expression, especially genes essential for myofibril formation and function. These transcripts were functional since numerous myofibrillar proteins were detected in discs using immunofluorescence. Interestingly, muscle genes whose expression is restricted to the adult stages were not activated in these adult myoblasts. These studies confirm a broad activation of the myogenic program in response to MEF2 expression and suggest that additional regulatory factors are required for promoting the adult muscle-specific program. These findings contribute to understanding the regulatory mechanisms governing muscle development and highlight the multifaceted role of MEF2 in orchestrating this intricate process. |
| Kim, J. H., Maruyama, R., Kim, K., Vertrees, D. A., Paul, P., Britson, K., Laughner, N. R., Andrew, D. J. (2025). Arc controls organ architecture through modulation of Crb and MyoII. J Cell Biol, 224(9) PubMed ID: 40504118
Summary: Precise orchestration of morphogenetic processes generates organs that are optimally positioned and the right size and shape to fit and maximize functionality. Arc, a large apical membrane-associated PDZ domain-containing protein, works through the apical determinant Crumbs to limit non-muscle myosin II (MyoII) activity during tissue invagination in the Drosophila salivary gland (SG). Loss of Arc, attenuation of Crumbs, and increased activation of MyoII leads to the simultaneous internalization of more precursor cells than normal. Consequently, mature SGs are shorter with more cells surrounding the lumen all along the tube. Correspondingly, overexpression of Arc or SG-specific knockdown of MyoII leads to longer SGs with fewer cells surrounding the lumen. These findings support a model wherein plasma membrane (PM)-associated Crumbs stabilizes cellular junctions by limiting apical pools of activated MyoII and countering the destabilizing effects of MyoII at the PM, limiting how many cells internalize at any given time, shaping final tube geometry. | Kyrchanova, O., Kudryashova, K., Ibragimov, A., Dubrovskaya, V., Schedl, P., Georgiev, P. (2025). Embryonic enhancers help transmit positional information to the initiator cores that control Drosophila Abd-B regulatory domains. Development, 152(19) PubMed ID: 41020347
Summary: Drosophila homeotic gene Abdominal-B (Abd-B) is controlled throughout development by four infraabdominal (iab) regulatory domains, the active or repressed state of which is determined by initiators that have parasegment-specific enhancer activity at an early stage of embryonic development. For this reason, it has long been assumed that the enhancer activity and initiation function of these elements are synonymous. This study examined two initiators that regulate the activity of the iab-5 and iab-6 domains responsible for Abd-B expression in embryonic parasegment PS10 (adult segment A5) and PS11(A6), respectively. In both initiators, core regions were identified that do not stimulate reporter gene transcription, but retain the ability to establish the appropriate activity state of the corresponding iab domains. Other initiator sequences are responsible for parasegment-specific reporter activation in early embryos and enhance the activity of the core initiators. Taken together, these results indicate that initiators represent a new type of regulatory element that function as on/off switches for regulatory domains controlling segment-specific Abd-B expression during Drosophila development. |
| Akaiwa, T., Oda, H., Akiyama-Oda, Y. (2025). Genome-wide quantitative dissection of an arthropod segmented body plan at single-cell resolution. Commun Biol, 8(1):913 PubMed ID: 40500297
Summary: Developmental processes underlying the characteristic segmented body plans in arthropods vary widely. While Drosophila is well-studied, few other arthropod species offer platforms for comparable genomics at single-cell resolution. This study presents high-quality quantitative data from single-nucleus RNA sequencing of spider Parasteatoda tepidariorum embryos at late stage 5 and stage 7, a critical period of emergence of segmental units along the anterior-posterior (AP) axis. Clustering analysis of the stage-7 dataset reconstructs an axial alignment of ectoderm cells, reflecting the differing cell states along the segmenting AP axis. This enables us to obtain genome-wide quantitative gene expression profiles along the reconstructed axis, which were used for unbiased and thorough molecular investigation of pattern elements employing statistical methods. Comprehensive gene-to-gene correlation analyses suggest distinct gene-regulatory interactions in different regions along the reconstructed axis. This study lays the foundation for exploring the origins of developmental diversity in the arthropod body plan. | Galouzis, C. C., Kherdjemil, Y., Forneris, M., Viales, R. R., Marco-Ferreres, R., Furlong, E. E. M. (2025). Chip (Ldb1) is a putative cofactor of Zelda forming a functional bridge to CBP during zygotic genome activation. Mol Cell, 85(12):2425-2441. PubMed ID: 40494353
Summary: The cofactor LIM-domain-binding protein 1 (Ldb1) is linked to many processes in gene regulation, including enhancer-promoter communication, interchromosomal interactions, and enhanceosome-cofactor-like activity. However, its functional requirement and molecular role during embryogenesis remain unclear. This study used optogenetics (iLEXY) to rapidly deplete Drosophila Ldb1 (Chip) from the nucleus at precise time windows. Remarkably, this pinpointed the essential window of Chip's function to just 1 h of embryogenesis, overlapping zygotic genome activation (ZGA). Zelda, a pioneer factor essential for ZGA, recruits Chip to chromatin, and both factors regulate concordant changes in gene expression, suggesting that Chip is a cofactor of Zelda. Chip does not significantly impact chromatin architecture at these stages, but instead recruits CBP, and is essential for H3K27ac deposition at enhancers and promoters, and for the proper expression of co-regulated genes. These data identify Chip as a functional bridge between Zelda and the coactivator CBP to regulate gene expression in early embryogenesis. |
Tuesday October 21st - Genes, RNAs and Proteins |
| Crava, C. M., Walker, W. B., 3rd, Cattaneo, A. M. (2025). Alternative strategies based on transgenic Drosophila melanogaster for the functional characterization of insect Ionotropic Receptors. Biol Res, 58(1):36 PubMed ID: 40490823
Summary: Activation of Ionotropic Receptors (IRs) has been studied by recording neuronal activity in situ, others by their heterologous expression in Xenopus oocytes or mis-expressing IRs from Drosophila melanogaster or from the related D. sechellia into the D. melanogaster "ionotropic receptor decoder" neuron, which lacks the endogenous tuning receptor subunit but expresses IR-coreceptors. In this study, use was made of Drosophila olfactory sensory neurons (OSNs) different from the "ionotropic receptor decoder", demonstrating that by replacing or introducing IRs alongside the native D. melanogaster ones, functional heteromeric complexes can be formed. IR41a1 from the lepidopteran Cydia pomonella exhibits binding to polyamines and the IR75d from the dipteran Drosophila suzukii binds hexanoic acid. Secondly, expressing D. suzukii's putative acid sensor IR64a into the "ionotropic receptor decoder" of D. melanogaster inhibits the response to the main activators of neighboring neurons from the same sensillum, despite that IR64a does not respond to acids. In situ hybridization on the antennae of D. suzukii unveils wide expression of IR64a in neurons proximal to the sacculus. Structural modeling analysis does not explain its absence of binding to acids; conversely, this approach identifies key amino acids features explaining the binding of hexanoic acid by IR75d. Finally, this study has also explored alternative methods to heterologously express IRs based on Human Embryonic Kidney cells (HEK293). Despite observing correct expression of IRs in transfected cells through immunohistochemistry experiments, this approach did not achieve successful deorphanization of these receptors. These findings highlight the potential use of Drosophila OSNs as a valuable tool for functional characterization of IRs from different insect species: for the first time, evidence is provided of IR-functionalities within alternative OSNs from the Drosophila's "ionotropic receptor decoder" neuron to functionally characterize and deorphanize IRs from lineages that are evolutionarily distant from the D. melanogaster subgroup, contributing to the understanding of chemosensory modalities in D. suzukii and C. pomonella, two globally significant agricultural pests. | Wang, T., Miao, J., Chang, Y., Liang, X., Li, F., Lu, H. (2025). Exploring novel insecticide candidates: Targeting Na(+),K(+) -ATPase in Drosophila melanogaster through computational and experimental approaches. J Mol Graph Model, 140:109111 PubMed ID: 40527194
Summary: Pest infestations have been posing a serious and persistent threat to agricultural production. Traditional insecticides are currently confronted with a multitude of problems. The discovery of novel insecticide targets and the screening of active molecules can offer an entirely new direction for surmounting the limitations of traditional insecticides and lay a solid foundation for the development of highly effective insecticides with distinctive mechanisms of action. In this study, the Na(+),K(+)-ATPase of Drosophila melanogaster has been selected as the target. Its three-dimensional structure has been constructed via homology modeling, and the evaluation has indicated that its quality is reliable. Subsequently, techniques including virtual screening, molecular docking, and molecular dynamics simulation have been employed to screen compounds and investigate their mechanisms of action. The analysis of binding modes has demonstrated that hydrogen bonding and hydrophobic interactions have played a crucial role in the binding of ligands. Molecular dynamics simulations and calculations of binding free energies have shown that Compound 1 and Compound 2 have exhibited similar or even stronger affinities in comparison to known inhibitors. Residue decomposition free energy reveals the types of key amino acid residues involved in the interaction between these compounds and NKA. Preliminary bioactivity assays have verified the bioactivities of these compounds. Ouabain, Compound 1, Compound 2, and Compound 4 have shown significant delayed toxic effects, with Compound 4 having a more pronounced delayed effect. Our study has provided certain valuable ideas and insights for the development of new insecticide molecules targeting the Na(+),K(+)-ATPase of Drosophila melanogaster. |
| Shah, N., Kovalchuk, V., Zerlotti, R., Cole, K., Bazzone, A., Sitte, H. H., Hummel, T., Kasture, A. S., Sucic, S. (2025). Rescue of Epilepsy-Associated Mutations of the Highly Conserved Glycine Residue 443 in the Human GABA Transporter 1. Faseb j, 39(11):e70614 PubMed ID: 40485335
Summary: The human γ-aminobutyric acid (GABA) transporter 1 (hGAT-1; see Drosophila Gat) plays a pivotal role in synaptic neurotransmission by facilitating the clearance of GABA from the synaptic cleft. Pathogenic mutations in the SLC6A1 gene encoding hGAT-1 have been implicated in a spectrum of neurodevelopmental disorders, including epilepsy, autism spectrum disorder, intellectual disability, and developmental delay. This study elucidated the molecular and functional consequences of disease-associated mutations affecting the highly conserved glycine residue at position 443 (G443) in hGAT-1. Through a combination of in vitro biochemical analyses, ion flux assays, and pharmacological profiling in HEK293 cells, alongside in vivo studies in Drosophila melanogaster, this study demonstrate that substitutions of G443 to aspartate (G443D) or valine (G443V) result in complete abolishment of GABA transport. This severe impairment stems from distinct disruptions in protein folding and trafficking. In particular, G443V is fully retained in the endoplasmic reticulum (ER), as substantiated by de-glycosylation assays indicating exclusively core-glycosylated protein bands and confocal co-localization with the ER chaperone calnexin. The G443D variant, on the other hand, exhibits partial trafficking to the plasma membrane, confirmed by the presence of maturely glycosylated bands, albeit at significantly reduced expression levels relative to the wild type transporter. Treatment with glycerol and 4-phenylbutyrate (4-PBA) successfully restored both surface expression and GABA uptake activity of the G443 mutants. These findings highlight the potential of small-molecule chaperones as interventions for ameliorating protein misfolding and functional deficits in hGAT-1-associated pathologies. | Shilova, V. Y., Garbuz, D. G., Chuvakova, L. N., Rezvykh, A. P., Funikov, S. Y., Davletshin, A. I., Sorokina, S. Y., Nikitina, E. A., Gorenskaya, O., Evgen'ev, M. B., Zatsepina, O. G. (2025). The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H(2)S in Drosophila melanogaster. Antioxidants (Basel), 14(6) PubMed ID: 40563325
Summary: This paper described the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H(2)S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H(2)S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies' fecundity and lifespan. These experiments exploring unique Drosophila strains with KO of major H(2)S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging. |
| Coulthard, A. B., Yuditskiy, R., Molnar, A. R., Ramazan, Q. A., Sokolowski, M. B., Hilliker, A. J. (2025). Alleles of Chaser, a dominant modifier of the Drosophila melanogaster foraging gene, are consistent with variegating alleles of the heterochromatic gene spookier. Genetics, PubMed ID: 40570000
Summary: The relationship between genes and quantitative behavioral traits involves complex regulatory networks. Identifying genes that operate in these regulatory pathways can be challenging, especially when dealing with dominant genetic factors. This work has focused on a naturally occurring behavioral polymorphism in larval foraging behavior in Drosophila melanogaster. This polymorphism in larval foraging behavior arises from variation in the foraging (for) gene with its rover and sitter naturally occurring variants. The dominant rover allele (forR) results in larvae which move longer distances while foraging compared to larvae with the recessive sitter (fors) alleles. This article reports the successful mapping of the Chaser (Csr) gene, a dominant modifier of larval foraging behavior which makes sitter larvae behave in a rover-like manner. Csr was localized by first mapping recessive phenotype tags closely linked to Csr. These phenotype tags mapped to the centromeric heterochromatin on the right arm of chromosome 3. A combination of deletion mapping, qRT-PCR and feeding of ecdysone hormone to larvae during development showed that the alleles of Csr are consistent with variegating alleles of the gene spookier (spok). With spok being an essential gene in the synthesis of the molting hormone ecdysone, this study has established a link between ecdysone signaling and larval foraging behavior in D. melanogaster. | Fudo, S., Verkhovskaya, M., Di Scala, C., Rivera, C., Kajander, T. (2025). Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate K(+)-Cl(-) cotransporters. FEBS Open Bio, PubMed ID: 40509965
Summary: The cation-chloride cotransporter (CCC) family includes ion symporters that cotransport monovalent cations and Cl(-), playing a crucial role in controlling cytoplasmic ion content. K(+)-Cl(-) cotransporters (KCCs) facilitate the symport of ions across the plasma membrane. The CCCs participate in various physiological processes, such as transepithelial ion transport and regulation of cell volume. Among KCCs, KCC2 has unique and essential functions in the central nervous system. KCC from Drosophila melanogaster (DmKCC) is an ortholog of mammalian KCCs. Its critical role in neuronal transmission has been demonstrated. Also, the cnidarian Hydra vulgaris has a functional KCC (HvKCC). Comparative analyses of these transporters with vertebrate counterparts can provide insights into the mechanism of KCC ion transport, regulation, and evolution. Thus, this study purified DmKCC and HvKCC and their biophysical properties were characterized using differential scanning fluorimetry and light scattering. Their functionality was evaluated in cells, developed a method was developed to study ion transport with flame photometry. Further, a fluorescence-based assay for DmKCC reconstituted into proteoliposomes was developed. The activity of DmKCC was found to be dependent on Ca(2+), which is reminiscent of some other chloride transport protein families and potentially important for the KCC protein family overall. |
Friday October 17th - Evolution |
| Musca, A. S., Ratiu, A. C., Ionascu, A., Constantin, N. D., Zahan, M. (2025). Short-Term Evolutionary Features and Circadian Clock-Modulated Gene Expression Analysis of Piezo, nanchung, and αTubulin at 67C in a Romanian Population of Drosophila suzukii. Insects, 16(6) PubMed ID: 40559021
Summary: Drosophila suzukii is a successful invasive insect species responsible for agricultural losses. The key to its prowess is the ability to swiftly adapt to new environments through various genetic mechanisms, including fast accommodation of mutations and gene expression fine-tuning. Piezo and nanchung (nan) genes are linked to circadian clock-related behaviors and, therefore, are expected to readily respond to stress stimuli. This study compared the DNA sequences of Piezo, nan, and αTubulin at 67C, a highly conserved housekeeping gene, in ICDPP-ams-1, a Romanian local population of D. suzukii, and two well-annotated reference populations from the United States of America and Japan. The results imply that short-term evolutionary accumulated single nucleotide and indel variants are overrepresented within introns, a propensity evaluated through the mutation accumulation tendency (MAT) original parameter. Piezo and nan gene expression under photoperiodicity changes challenges were assessed in a series of experiments on three groups of individuals from ICDPP-ams-1. Both genes are upregulated in females if their customary circadian rhythm is affected, a trend seemingly reverting if, after an initial perturbation, the circadian clock is reset to its initial timing. In conclusion, this study found that both highly conserved and adaptability-related genes are rapidly evolving and that Piezo and nan have a fast functional reaction to circadian clock changes by modifying their gene expression profiles. | Fan, T., Cridland, J. M., Begun, D. J. (2025). Adaptive gene expression parallelism in the male reproductive tract of two Drosophila species. Genetics, PubMed ID: 40492850
Summary: While stabilizing selection, which promotes a monomorphic population, is likely an important process leading to conserved phylogenetic patterns of gene expression, the role of selection in driving expression divergence amongst populations and species is much less clear. One approach for identifying adaptation is to document parallel evolution, the independent evolution of similar phenotypes in multiple species in response to similar selective pressures. Latitudinal clines are a classic system for studying adaptation in many species, including Drosophila; multiple species exhibit clines for several phenotypes, such as body and wing size. However, the extent of latitudinal transcriptome variation and the degree to which such variation is shaped by selection remain unclear. Here, we investigate transcriptomes of North American D. melanogaster and D. simulans with a focus on the male reproductive tract. For both species accessory glands and testis were sampled from lines derived from two locations, one low latitude (Panama City, Panama), and one high latitude (Maine, USA). We observed a striking similarity between species in the directionality and magnitude of latitudinal expression variation in the accessory gland but not in the testis. This suggests that selection has fine-tuned accessory gland transcript abundance in a similar manner in response to latitudinal selection pressures in both species. In addition to gene level parallelism, these species exhibit correlated fluctuations of high vs. low latitude expression differences on a larger chromosomal scale. Analysis of whole male transcriptomes from the same population samples suggests that parallel latitudinal selection responses play an important role in expression adaptation for both species. |
| Crowley-Gall, A., Layne, J. E., Ammagarahalli, B., Hamrick, A. A., Lawson, L. P., Rollmann, S. M. (2025). Olfactory variation among closely related cactophilic Drosophila species. J Comp Physiol A Neuroethol Sens Neural Behav Physiol, PubMed ID: 40504427
Summary: Chemosensation plays an important role in a wide range of behaviors including host identification and localization, oviposition site selection, and mate recognition. Variation in the ability to detect chemical signals may influence behavior in animals like insects that use volatile cues emitted from plants when discriminating between potential hosts. Differences in odor detection has been demonstrated to play a crucial role in driving changes in host use within and between insect species, leading to reproductive isolation between populations and eventual speciation through specialized host adaptation. We examined between-species variation in odor tuning and asked whether it is linked to shifts in host plant use in the Drosophila repleta species group, a taxonomic radiation of flies specializing on cacti that exhibits multiple shifts in host plant use across their phylogeny resulting in three current states: (1) Opuntia cactus specialists, (2) columnar cactus specialists, and (3) cactus "generalists" which use both hosts. We measured odor response profiles from select olfactory sensillar subtypes across multiple species within the group as well as for the outgroup D. melanogaster. Variation in both sensitivity and specificity to odors was observed, with some olfactory sensory neurons exhibiting differences associated with host cactus use. This study is the first in-depth analysis of the olfactory system across the repleta species group and provides the opportunity to test for conserved mechanisms in the olfactory system underlying divergence and host shift. | Church, S. J., Kriebel, A. R., Welch, J. D., Buttitta, L. A. (2025). Evidence for Transcriptomic Conservation Between the Main Cells of the Drosophila Prostate-Like Accessory Gland and Basal Cells of the Mammalian Prostate. bioRxiv, PubMed ID: 40501690
Summary: The Drosophila accessory gland performs functions analogous to the mammalian prostate in production of seminal fluid components that are essential for male fertility. The mammalian prostate and Drosophila accessory glands share a similar tissue organization and structure. Both organs contain secretory epithelial cells forming a gland lumen, surrounded by a stroma with extracellular matrix enveloped by innervated muscle for organ contraction and fluid release. However, the Drosophila accessory gland secretory epithelium is postmitotic, polyploid and binucleate, and lacks a known stem cell population. By contrast, the mammalian prostate epithelium is made up of diploid luminal secretory cells and diploid basal cells that are maintained by at least two stem cell populations. Despite the differences in the tissues, it has been argued these tissues may share a 'deep homology' based on the expression of conserved genes during development. This study performed a cross-species comparative analysis using single-cell RNA sequencing data from adult tissues using data from the Drosophila Fly Cell Atlas and mammalian adult prostate single-cell datasets. This analysis provides additional evidence of transcriptomic similarity between the main epithelial cells of the Drosophila prostate-like accessory gland and the basal epithelial cells of the mammalian prostate. While it is unknown whether these similarities reflect shared evolutionary homology, or independently derived features due to shared tissue functions, the results strengthen the arguments that the Drosophila accessory gland can be used to effectively model aspects of human prostate biology and disease. |
| Senti, K. A., Rafanel, B., Handler, D., Kosiol, C., Schlotterer, C., Brennecke, J. (2025). Co-evolving infectivity and expression patterns drive the diversification of endogenous retroviruses. Embo j, PubMed ID: 40474005
Summary: Transposable elements are major contributors to the evolution of their hosts, but the mechanisms driving their own diversification remain poorly understood. This study reveals key principles governing the evolution of insect endogenous retroviruses (ERVs), a class of infectious LTR-retrotransposons that encode an Envelope protein. Through comparative analyses and experimental studies of transposon replication cycles in Drosophila, this study demonstrates how two crucial ERV traits-infectivity and spatiotemporal expression-co-evolve. ERVs have adapted their cis-regulatory sequences to function across all ovarian cell types. Strikingly, infectious ERV lineages display distinct expression patterns in somatic cells, from where they infect the germline, whereas derived retroelement lineages that have lost infectivity are expressed exclusively in the germline. Co-evolutionary changes in the piRNA pathway, which integrates transposon promoter and sequence information into differentially expressed piRNA clusters, highlight the functional significance of the diverse ERV expression niches. By investigating a unique ERV lineage, rover, this study reconstructed the molecular events that transformed an infectious ERV into a retroelement. Overall, this study uncovers fundamental mechanisms that drive the co-evolution of ERVs and their hosts, with important implications for understanding the functional diversification of LTR sequences. | Bensaha, S., Lewandowska, D., Muzzopappa, F., Hutin, S., Tully, M. D., Anfossi, M., Cammas, F. M., Normand, C., Erdel, F. (2025). HP1 loses its chromatin clustering and phase separation function across evolution. Nat Commun, 16(1):6375 PubMed ID: 40640210
Summary: Heterochromatin protein 1 (HP1) is a multifunctional chromatin-associated protein conserved from fission yeast to mammals. HP1 has been suggested to drive heterochromatin formation via phase separation. However, there is seemingly conflicting evidence about HP1 phase-separating in different systems or not. This study assessed the phase separation behavior of HP1 from fission yeast, fruit fly and mouse in vitro and in mammalian cells side-by-side. HP1 from fission yeast and fly can undergo liquid-liquid phase separation and induce heterochromatin coalescence in mouse cells, in stark contrast to HP1 from mouse. Induced heterochromatin coalescence has only mild effects on gene expression. This study linked the decreasing phase separation propensity of HP1 homologs to their decreasing intrinsic disorder and their increasing sensitivity to HP1 paralogs antagonizing phase separation. This work elucidates the relationship between phase separation, nuclear organization and gene expression, and highlights the evolutionary dimension of protein phase separation control. |
Wednesday October 15th - Metabolism and Physiology |
| Giang, A., Martelli, F., Fusetto, R., Nero, T. L., Lueke, B., Nauen, R., Batterham, P. (2025). Functional and structural insights into P450-mediated resistance: The role of Cyp6g1 and Cyp6g2 in the metabolism of neonicotinoids in Drosophila melanogaster. Pestic Biochem Physiol, 212:106451 PubMed ID: 40500059
Summary: Insecticide-driven selection pressures have accelerated the evolution and widespread emergence of resistance in insect populations. A major mechanism underlying this resistance is the enhanced metabolic detoxification of insecticides, often mediated by the overexpression or increased activity of cytochrome P450 enzymes. Evidence indicates that the ability of these enzymes to confer resistance may have evolved from their native role in metabolising environmental xenobiotics. This suggests that insect populations may harbor multiple metabolic enzymes capable of conferring resistance, even if not specifically adapted for insecticide metabolism. To investigate this hypothesis, the well-characterised resistance gene Cyp6g1 and five closely related cytochrome P450s were examined in Drosophila melanogaster. Using transgenic overexpression driven by the Accord promoter-responsible for elevated Cyp6g1 expression in natural populations-this study found that only Cyp6g1 and Cyp6g2 conferred resistance to the neonicotinoids imidacloprid and nitenpyram. Metabolic assays confirmed that imidacloprid resistance was mediated by the conversion of imidacloprid into 5-hydroxyimidacloprid. Additionally, field-resistant haplotypes promoting Cyp6g1 overexpression were also found to increase Cyp6g2 expression, suggesting that Cyp6g2 contributes to resistance in natural populations. Structural analysis of CYP6G1, using molecular docking and site-directed mutagenesis, identified residues Phe123 and Phe124 as critical for imidacloprid metabolism. These findings contribute to understanding of the evolutionary pathways leading to metabolic resistance and offer insights that could improve strategies for managing and mitigating insecticide resistance. | Comeault, A. A., Orta, A. H., Fidler, D. B., Nunn, T., Ellison, A. R., Anspach, T. A., Matute, D. R. (2025). Phylogenetic and functional diversity among Drosophila-associated metagenome-assembled genomes. mSystems:e0002725 PubMed ID: 40600712
Summary: Host-associated microbial communities can mediate interactions between their hosts and biotic and abiotic environments. While much work has been done to document how microbiomes vary across species and environments, much less is known about the functional consequences of this variation. This study tested for functional variation among drosophilid-associated bacteria by conducting Oxford Nanopore long-read sequencing and generating metagenome-assembled genomes (MAGs) from communities associated with six species of drosophilid flies collected from "anthropogenic" environments in North America, Europe, and Africa. Using phylogenetic analyses, this study found that drosophilid flies harbor a diverse microbiome that includes core members closely related to the genera Gilliamella, Orbus, Entomomonas, Dysgonomonas, and others. Comparisons with publicly available bacterial genomes show that many of these genera are associated with phylogenetically diverse insect gut microbiomes. Using functional annotations and predicted secondary metabolite biosynthetic gene clusters, this study shows that MAGs belonging to different bacterial orders and genera vary in gene content and predicted functions, including metabolic capacity and how they respond to environmental stressors. The results provide evidence that wild drosophilid flies harbor phylogenetically and functionally diverse microbial communities. These findings highlight a need to quantify the abundance and function of insect-associated bacteria from the genera Gilliamella, Orbus, Entomomonas, and others on the performance of their insect hosts across diverse environments (Comeault, 2025). |
| Daplan, E., Rodriguez, E., Lane, N., Turin, L. (2025). A chance insight into phosgene toxicity Free Radic Biol Med, 238:113-122 PubMed ID: 40550401
Summary: It has long been known that phosgene, a war gas and an industrial reagent, causes intense oxidative stress, but how it does so remains unclear. Here we report an accidental discovery: Electron spin resonance spectroscopy (ESR) of live fruit flies reveals that phosgene exposure results in a distinctive manganese (II) hyperfine structure. After exposure to phosgene, every batch of flies consistently displays the Mn (II) signal. Regardless of the aftercare provided, these flies inevitably perish, making the signal a diagnostic of phosgene poisoning in flies. The intensity of the signal is dependent on both exposure time and concentration, resembling the kinetics of phosgene poisoning. The signal of Mn (II) correlates with the presence of a functional superoxide dismutase Sod2. After exposure, heterozygous Sod2 mutants have a markedly lower intensity of Mn (II) in their ESR spectrum. Phosgene is suggested to disturb Mn redox cycling between ESR-silent Mn (III) and ESR-active Mn (II) that is required for superoxide dismutation. Accordingly,mitochondria of phosgene-treated flies show reduced rates of hydrogen peroxide production, and severely compromised complex I-linked respiration. It is likely that phosgene damages mitochondria through MnSOD and complex I, which contributes to its toxicity. This work uses Drosophila melanogaster for the first time in phosgene research. | Chen, H. Y., Wu, P. S., Li, Z. Y., Liu, Y. C., Yeh, S. R., Duan, B. C., Cheng, K. W., Hsu, C. C., Chiu, Y. L., Lee, W. T., Fan, S. Z., Wang, P. Y. (2025). Gut microbiome and host TOR pathway interact to regulate predator-induced aversive memory in Drosophila melanogaster. Proc Natl Acad Sci U S A, 122(25):e2422928122 PubMed ID: 40540603
Summary: The gut microbiome has emerged as a key factor influencing a wide range of host physiological processes and behaviors, though the mechanisms behind these effects remain only partially understood. This study explored the role of the gut microbiome in memory regulation using a parasitoid wasp-induced oviposition depression paradigm in Drosophila melanogaster. The findings show that flies with depleted gut microbiota, either through axenic culture or antibiotic treatment, exhibited significant memory impairments. However, reintroducing the commensal bacterium Lactobacillus plantarum alone was sufficient to restore memory, while coinoculation with Acetobacter pomorum further enhanced memory performance. Hemolymph metabolomic analyses revealed reduced amino acid levels in antibiotic-treated flies, which were linked to impaired Drosophila target of rapamycin (dTOR) signaling. Additionally, genetic manipulation of dTOR or dietary supplementation with branched-chain amino acids either mimicked or rescued the memory deficits caused by antibiotic treatments. These results suggest that the gut microbiome is essential for regulating memory function by maintaining amino acid homeostasis and proper dTOR signaling, with profound implications for advancing knowledge of cognitive regulation. |
| Vega-Cuesta, P., Pulido, D., Abia, D., Herrera, S., Lopez-Varea, A., Ruiz-Gomez, A., Fernandez-Freire, P., Peropadre, A., de Celis, J. F. (2025). A Drosophila ecdysone-deficient model to assess the endocrine disruptor activity of Bisphenol A. Ecotoxicol Environ Saf, 300:118483 PubMed ID: 40499484
Summary: Bisphenol A (BPA) is a well characterized endocrine disruptor that interferes with the activity of a variety of nuclear receptors. For this reason, BPA has the potential to impact the function of the endocrine system and alter cellular physiology. This study presents a novel experimental system to characterize the actions of dietary BPA on organism physiology. Drosophila melanogaster larvae genetically deficient for the synthesis of the major insect steroid hormone, ecdysone, were used. These larvae exhibit a variety of phenotypes that can be rescued by dietary supplementation of 20-hydroxy-ecdysone or Ponasterone A, a naturally occurring ecdysteroid. The effect of different concentrations of BPA exposure were tested in this genetic background, and this chemical was found to partially rescues the deficit in ecdysone. Furthermore, through in silico structural predictions of the Ecdysone receptor's ligand binding domain, a protein domain was identified capable of accommodating with different affinities ecdysone, Ponasterone A and BPA molecules. These findings pave the way for novel experimental approaches to identify and characterize new potential vertebrate endocrine disruptors. | Burgmer, S., Meyer Zu Altenschildesche, F. L., Gyenis, A., Lee, H. J., Vilchez, D., Giavalisco, P., Fichant, A., Uhlirova, M., Storelli, G. (2025). Endosymbiont control through non-canonical immune signaling and gut metabolic remodeling. Cell Rep, 44(6):115811 PubMed ID: 40483691
Summary: Animals coexist with bacteria and need to keep these microorganisms under tight control. To achieve such control, pattern recognition receptors (PRRs) sense bacterial cues and induce the production of antimicrobials. Here, we uncover a metabolic arm in the control of symbionts by PRRs. In Drosophila, the PRRs PGRP-LC and PGRP-LE act independently of canonical NF-NFkappaB signaling to repress essential metabolic functions in the gut, such as digestion and central carbon metabolism. This metabolic switch affects commensal populations and drastically reduces intestinal and systemic populations of the intracellular parasite Wolbachia. It is proposed that intestinal metabolic remodeling complements immune responses by imposing nutrient restriction on intracellular bacteria, whose lifestyle protects them from antimicrobials.These findings reveal a role for PRRs in bacterial control beyond canonical immune pathways and provide insights into how microbial signals modulate symbiotic populations but also nutrition and metabolism in animals (Burgmer, 2025). |
Friday October 10th - Gonads |
| Church, S. J., Kriebel, A. R., Welch, J. D., Buttitta, L. A. (2025). Evidence for Transcriptomic Conservation Between the Main Cells of the Drosophila Prostate-Like Accessory Gland and Basal Cells of the Mammalian Prostate. bioRxiv, PubMed ID: 40501690
Summary: The Drosophila accessory gland performs functions analogous to the mammalian prostate in production of seminal fluid components that are essential for male fertility. The mammalian prostate and Drosophila accessory glands share a similar tissue organization and structure. Both organs contain secretory epithelial cells forming a gland lumen, surrounded by a stroma with extracellular matrix enveloped by innervated muscle for organ contraction and fluid release. However, the Drosophila accessory gland secretory epithelium is postmitotic, polyploid and binucleate, and lacks a known stem cell population. By contrast, the mammalian prostate epithelium is made up of diploid luminal secretory cells and diploid basal cells that are maintained by at least two stem cell populations. Despite the differences in the tissues, it has been argued these tissues may share a 'deep homology' based on the expression of conserved genes during development. This study performed a cross-species comparative analysis using single-cell RNA sequencing data from adult tissues using data from the Drosophila Fly Cell Atlas and mammalian adult prostate single-cell datasets. This analysis provides additional evidence of transcriptomic similarity between the main epithelial cells of the Drosophila prostate-like accessory gland and the basal epithelial cells of the mammalian prostate. While we do not know whether these similarities reflect shared evolutionary homology, or independently derived features due to shared tissue functions, the results strengthen the arguments that the Drosophila accessory gland can be used to effectively model aspects of human prostate biology and disease. | Nunes, R. D., Drummond-Barbosa, D. (2025). Brain dopamine imbalance causes follicle death and underlies negative effect of high sugar diet during Drosophila oogenesis. bioRxiv, PubMed ID: 40510569
Summary: Unhealthy diets, obesity, and low fertility are associated in Drosophila and humans. Previous work showed that a high sugar diet, but not obesity, reduces Drosophila female fertility owing to increased death of newly formed germline cysts and vitellogenic follicles. Drosophila strains carrying mutations in the yellow ( y ) and white ( w ) pigmentation genes are routinely used for investigating the effects of high sugar diets, but it has remained unclear how this genetic background interacts with high sugar. This study shows that wildtype females retain normal fertility on high sugar compared to control diets, and that mutation of y is responsible for the previously observed vitellogenic follicle death on high sugar. The known requirement of y for melanin biosynthesis from dopamine, as well as the association between high sugar consumption and reduced dopamine in mammals and decreased dopamine responses in male Drosophila, prompted an investigation into potential connections between y, high sugar, dopamine and oogenesis. Global impairment was found of dopamine metabolism leads to vitellogenic follicle degeneration while alleviating dopamine imbalance in y mutant females prevents follicle death on a high sugar diet. Finally, lack of dopamine production in the central nervous system is sufficient for vitellogenic follicle death on a high sugar diet, and severe dopamine imbalance causes follicle death regardless of diet or genetic background. These findings are broadly relevant to our understanding of how the effects of unhealthy diets might differ depending on genetic factors and highlight a key connection between brain dopamine metabolism and ovarian follicle survival. |
| Das, S., Roy, A. E., K, K., Deshpande, G., Ratnaparkhi, G. S. (2025). Caspar modulates primordial germ cell fate both in Oskar-dependent and Oskar-independent manner. Biol Open, PubMed ID: 40614258
Summary: Primordial Germ Cell (PGC) formation and specification is a fundamental conserved process as PGCs are the progenitors of germline stem cells (GSCs). In Drosophila melanogaster, maternally deposited Oskar (Osk) and ccentrosome dynamics are two independent determinants of PGC fate. Caspar, Drosophila homolog of Fas-associated factor 1 (FAF1), promotes PGC formation/specification and maintains the PGC count by modulating both the Osk levels and centrosome function. Consistently, casplof PGCs display reduction and inefficient release/ transmission of germ plasm. Defective centrosome migration and behavior are evident even prior to PGC formation engineered by Osk and its targets. Taken together with the inability of Osk to regulate nuclear and centrosome migration, these data demonstrate that Casp encodes a novel bi-modal regulator of PGC fate as it controls Osk levels likely by downregulating translational repressor, Smaug (Smg) and also influences nuclear/centrosome migration during early mitotic nuclear division cycles (NCs 6-9) which are Osk-independent. Dual functionality of Casp vis-a-vis germline/soma segregation is discussed as it helps acquire both the PGCs and the surrounding soma their individual identities. | Anderson, M. T., Horne-Badovinac, S. (2025). A complex relationship between the architecture of the basement membrane, its mechanical properties, and its ability to shape the Drosophila egg. Matrix Biol, PubMed ID: 40518025
Summary: Basement membranes (BMs) are planar extracellular matrices that line the basal surfaces of epithelia and are essential components of most organs. During development, BMs can also play instructive roles in shaping the tissues to which they belong, but how they do so is incompletely understood. The Drosophila egg chamber has become a premier system to study this aspect of BM biology due to the ostensible simplicity of the BM's role in morphogenesis. The prevailing model posits that the egg chamber's outer layer of epithelial cells creates a symmetric stiffness gradient in the surrounding BM that preferentially channels egg chamber growth along one axis to create the elongated shape of the egg. There is evidence that the stiffening of the BM depends, in part, on a polarized array of fibrils that form within the BM network, and yet the exact role the BM fibrils play in egg chamber elongation has remained unclear. This study used genetic conditions that abrogate fibril formation to different extents to probe the relationship between the BM's fibril content, its mechanical properties, and the shape of the egg. The results of these experiments are consistent with a model in which BM fibrils influence egg shape by directly augmenting the mechanical properties of the BM. However, a final genetic condition was examined that does not fit this simple narrative. It is proposed that the role of the BM in conferring final egg shape is more complicated than previously thought and that some approaches used to study this role should be re-evaluated for their efficacy. |
| Andreatta, G., Montagnese, S., Costa, R. (2025). Cold-Sensing TRP Channels and Temperature Preference Modulate Ovarian Development in the Model Organism Drosophila melanogaster. Int J Mol Sci, 26(12) PubMed ID: 40565102
Summary: Temperature is perceived primarily via transient receptor potential (TRP) channels, which are integral to the molecular machinery sensing environmental and cellular signals. Functional evidence of TRP channels' involvement in regulating cold-induced developmental/reproductive responses remains scarce. This study shows that mutations affecting cold-sensing TRP channels antagonize the reduction in ovarian development induced by low temperatures (reproductive dormancy) in Drosophila melanogaster. More specifically, mutants for brv1, trp, and trpl significantly lowered dormancy levels at 12 °C and exhibited well-developed oocytes characterized by advanced vitellogenesis. Similarly, functional knockouts for norpA, a gene encoding a phospholipase C acting downstream to Trp and Trpl, exhibited a reduced dormancy response, suggesting that Ca(2+) signaling is key to relaying cold-sensing stimuli during dormancy induction and maintenance. Finally, mutants with an altered temperature preference (i.e., exhibiting impaired cold or warm avoidance) differentially responded to the cold, either lowering or increasing dormancy levels. In summary, this phenotypic analysis provides functional evidence of developmental/reproductive modulation by specific cold-sensing TRP channels in Drosophila melanogaster and indicates that temperature preference affects developmental processes. | Bischoff, M. C., Norton, J. E., Clark, S. E., Peifer, M. (2025). Plexin/Semaphorin antagonism orchestrates collective cell migration and organ sculpting by regulating epithelial-mesenchymal balance. Sci Adv, 11(25):eadu3741 PubMed ID: 40532000
Summary: Cell behavior emerges from the intracellular distribution of properties such as protrusion, contractility, and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture, orchestrating self-regulation during development, wound healing, and cancer progression. The Drosophila testis-nascent-myotube system that allows dissection of contact-dependent migration in vivo at high resolution. This study describes a role for the axon guidance factor Plexin A in collective cell migration: maintaining cell-cell interfaces at a precise point on the mesenchymal-to-epithelial continuum. This is crucial for testis myotubes to migrate as a continuous sheet, allowing normal sculpting-morphogenesis. Cells must maintain filopodial N-cadherin-based junctions and remain ECM-tethered near cell-cell contacts to spread while collectively moving. These data further suggest Semaphorin 1b is a Plexin A antagonist, fine-tuning activation. This reveals a contact-dependent mechanism to maintain sheet integrity during migration, driving organ morphogenesis. This is relevant for mesenchymal organ sculpting in other migratory contexts such as angiogenesis. |
Thursday October 9th - Behavior |
| Shih, M. M., Zhang, J., Brown, E. B., Dubnau, J., Keene, A. C. (2025). Targeted single cell expression profiling identifies integrators of sleep and metabolic state. G3 (Bethesda), 15(7) PubMed ID: 40509864
Summary: Animals modulate sleep in accordance with their internal and external environments. Metabolic cues are particularly potent regulators of sleep, allowing animals to alter their sleep timing and amount depending on food availability and foraging duration. The fruit fly, Drosophila melanogaster, suppresses sleep in response to acute food deprivation, presumably to forage for food. This process is dependent on a single pair of Lateral Horn Leucokinin (LHLK) neurons, that secrete the neuropeptide Leucokinin. These neurons signal to insulin producing cells and suppress sleep under periods of starvation. The identification of individual neurons that modulate sleep-metabolism interactions provides the opportunity to examine the cellular changes associated with sleep modulation. This study used single-cell sequencing of LHLK neurons to examine the transcriptional responses to starvation. A targeted single-cell sequencing approach was shown to selectively isolate RNA from individual LHLK neurons. Single-cell CEL-Seq comparisons of LHLK neurons between fed and 24-h starved flies identified 24 genes that are differentially expressed in accordance with starvation state. In total, 12 upregulated genes and 12 downregulated genes were identified. Gene-ontology analysis showed an enrichment for Attacins, a family of antimicrobial peptides, along with a number of transcripts with diverse roles in regulating cellular function. Targeted knockdown of differentially expressed genes identified multiple genes that function within LHLK neurons to regulate sleep-metabolism interactions. Functionally validated genes include an essential role for the E3 ubiquitin ligase insomniac, the sorbitol dehydrogenase Sodh1, as well as AttacinC and AttacinB in starvation-induced sleep suppression. Taken together, these findings provide a pipeline for identifying novel regulators of sleep-metabolism interactions within individual neurons. | Okuyama, T., Sato, D. X., Takahashi, Y. (2025). Genetic heterogeneity induces non-additive behavioural changes in Drosophila. J Exp Biol, 228(11) PubMed ID: 40485216
Summary: The formation and dynamics of group behaviours are important topics in ecology and evolution. Although several theoretical studies assume homogeneity among individuals, real-world organisms often display remarkable behavioural diversity within groups. This study investigated the synergistic impact of genetic heterogeneity on group behaviour and revealed the behavioural underpinnings of diversity effects using 83 genetically distinct strains of Drosophila melanogaster. Various indices of exploratory behaviour, including movement speed, search comprehensiveness, spatial preference and stopping time, were measured using homogeneous (single strain) and heterogeneous (mixing two distinct strains) groups of flies. The heterogeneous groups exhibited significant differences in spatial preference and stopping time compared with the homogeneous groups, suggesting that genetic heterogeneity induces non-additive changes in group behaviour. Furthermore, the magnitude and direction of the behavioural change varied among different combinations. Multiple regression analysis showed that the phenotypic distance in some traits between mixed strains could explain the emergence of diversity effects on group behaviour. Specifically, interindividual heterogeneity in the locomotor activity level showed a positive correlation with diversity effects. These results emphasise the importance of intraspecific diversity in group dynamics and suggest that genetic heterogeneity can improve group performance through the acquisition of latent behavioural traits. |
| Otarola-Jimenez, J., Spehr, R., Hansson, B. S., Knaden, M. (2025). How Sugar Quality and Concentration Influence Oviposition Preference in Drosophila Melanogaster. J Chem Ecol, 51(4):67 PubMed ID: 40540140
Summary: Female insects possess a complex chemosensory system that enables them to identify optimal oviposition substrates for their developing offspring. Both calorie-rich and protein-rich substrates are particularly attractive for laying eggs. Females were hypothesized to detect concentrations of sweet compounds and preferentially select those concentrations that enhance larval survival. To test this, how female Drosophila melanogaster evaluate substrates was explorted varying concentrations of sugars and amino acids, and whether these preferences correlate with larval survival was teste. Using choice assays, this study found that females preferentially deposited eggs on substrates containing 0.1 Mol/L sucrose, while higher concentrations (2 mol/L) were consistently avoided-a response not attributable to differences in substrate hardness or prior feeding experience during mating. In contrast, when presented with monosaccharides, females favored intermediate concentrations: 0.5 mol/L for both glucose and fructose, with a marked overall preference for fructose even when combined with an amino acid mixture. Moreover, substrates aligning with the females' oviposition choices often supported best survival of larvae. These findings indicate that female flies assess not only the concentration but might also consider the chemical nature of sweet compounds when making oviposition decisions and they underscore a critical link between maternal site selection and larval development. | Choton, T., Arun, M. G., Durga, H., Jaswal, P., Prasad, N. G. (2025). Housing density affects the survivorship post infection of Drosophila melanogaster males in a pathogen dependent manner. J Invertebr Pathol, 212:108395 PubMed ID: 40623622
Summary: The impact of social interaction on physiology and behaviour has been widely studied in social insects, but less so in non-eusocial insects. Group housing can signal higher infection risk and reproductive competition, potentially leading to context-dependent trade-offs between reproductive versus immune investment. In this study, Drosophila melanogaster males were housed singly or in groups of two or sixteen for two days, and their post infection survival was assessed. Singly held males exhibited higher mortality post-infection with Pseudomonas entomophila compared to males housed in groups of sixteen. Males held singly or as pairs did not significantly differ in their mortality. However, there was no difference in mortality between the three groups when the pathogen was Bacillus thuringiensis. Singly held males showed elevated levels of cat1, sod and puc and lower levels of rel, indicating elevated stress levels and lower immunity in them. Environmental factors other than the housing density did not account for the difference in survivorship between singly held and group-held flies post-infection with P. entomophila. No trade-off was observed between reproductive investment and post-infection survivorship. Thus, these results show a complex interplay between social isolation, stress related mechanisms and immune function of a non-eusocial insect. |
| Arntsen, C., Grenon, J., Chauvel, I., Fraichard, S., Dupas, S., Cortot, J., Audette, K., Musso, P. Y., Stanley, M. (2025). Artificial sweeteners differentially activate sweet and bitter gustatory neurons in Drosophila. Sci Rep, 15(1):20785 PubMed ID: 40594804
Summary: Artificial sweeteners are highly sweet, non-nutritive compounds that have become increasingly popular over recent decades despite research suggesting that their consumption has unintended consequences. Specifically, there is evidence suggesting that some of these chemicals interact with bitter taste receptors, implying that sweeteners likely generate complex chemosensory signals. This study reports the basic sensory characteristics of sweeteners in Drosophila, a common model system used to study the impacts of diet. All noncaloric sweeteners inhibited appetitive feeding responses at higher concentrations. At a cellular level, sucralose and rebaudioside A co-activated sweet and bitter gustatory receptor neurons (GRNs), two populations that reciprocally impact feeding behavior, while aspartame only activated bitter cells. The behavioral impacts of sweet and bitter co-activation were assessed; low concentrations of sucralose were found to signal appetitive feeding while high concentrations signal feeding aversion. Finally, silencing bitter GRNs reduced the aversive signal elicited by high concentrations of sucralose and significantly increased sucralose feeding behaviors. Together, it is concluded that artificial sweeteners generate a gustatory signal that is more complex than "sweetness" alone, and this bitter co-activation has behaviorally relevant effects on feeding that may help flies flexibly respond to these unique compounds. | Collie, M. F., Jin, C., Kellogg, E., Vanderbeck, Q. X., Hartman, A. K., Holtz, S. L., Wilson, R. I. (2025). Specialized parallel pathways for adaptive control of visual object pursuit. bioRxiv, PubMed ID: 40599160
Summary: To pursue an unpredictably moving visual object, the brain must generate motor commands that continuously steer the object to the midline of the visual field via feedback. Behavior implies that visual pursuit relies on a feedback loop with flexible gain, but the mechanisms of this "adaptive control" are not well-understood. This study shows that adaptive control in the Drosophila pursuit system involves two parallel feedback loops. One serves to steer the object coarsely toward the midline; the properties of this pathway are relatively constant. The other functions to steer the object precisely to the midline, and its properties are flexible: gain increases when the object is moving away from the midline, when the pursuer is running fast, and during arousal. Genetically suppressing this flexible pathway decreases pursuit performance in aroused males. These findings show how biological feedback systems can implement adaptive control to drive vigorous error correction while avoiding instability. |
Monday October 6th - RNAs and Transposons |
| Comeault, A. A., Orta, A. H., Fidler, D. B., Nunn, T., Ellison, A. R., Anspach, T. A., Matute, D. R. (2025). Phylogenetic and functional diversity among Drosophila-associated metagenome-assembled genomes. mSystems:e0002725 PubMed ID: 40600712
Summary: Host-associated microbial communities can mediate interactions between their hosts and biotic and abiotic environments. While much work has been done to document how microbiomes vary across species and environments, much less is known about the functional consequences of this variation. This study tested for functional variation among drosophilid-associated bacteria by conducting Oxford Nanopore long-read sequencing and generating metagenome-assembled genomes (MAGs) from communities associated with six species of drosophilid flies collected from "anthropogenic" environments in North America, Europe, and Africa. Using phylogenetic analyses, this study found that drosophilid flies harbor a diverse microbiome that includes core members closely related to the genera Gilliamella, Orbus, Entomomonas, Dysgonomonas, and others. Comparisons with publicly available bacterial genomes show that many of these genera are associated with phylogenetically diverse insect gut microbiomes. Using functional annotations and predicted secondary metabolite biosynthetic gene clusters, this study shows that MAGs belonging to different bacterial orders and genera vary in gene content and predicted functions, including metabolic capacity and how they respond to environmental stressors. The results provide evidence that wild drosophilid flies harbor phylogenetically and functionally diverse microbial communities. These findings highlight a need to quantify the abundance and function of insect-associated bacteria from the genera Gilliamella, Orbus, Entomomonas, and others on the performance of their insect hosts across diverse environments. | Daplan, E., Rodriguez, E., Lane, N., Turin, L. (2025). A chance insight into phosgene toxicity. Free Radic Biol Med, 238:113-122 PubMed ID: 40550401
Summary: It has long been known that phosgene, a war gas and an industrial reagent, causes intense oxidative stress, but how it does so remains unclear. This study reports an accidental discovery: Electron spin resonance spectroscopy (ESR) of live fruit flies reveals that phosgene exposure results in a distinctive manganese (II) hyperfine structure. After exposure to phosgene, every batch of flies consistently displays the Mn (II) signal. Regardless of the aftercare provided, these flies inevitably perish, making the signal a diagnostic of phosgene poisoning in flies. The intensity of the signal is dependent on both exposure time and concentration, resembling the kinetics of phosgene poisoning. The signal of Mn (I() correlates with the presence of a functional superoxide dismutase Sod2. After exposure, heterozygous Sod2 mutants have a markedly lower intensity of Mn (II) in their ESR spectrum. Phosgene is thought to disturbs Mn redox cycling between ESR-silent Mn (III) and ESR-active Mn (II) that is required for superoxide dismutation. Accordingly, mitochondria of phosgene-treated flies show reduced rates of hydrogen peroxide production, and severely compromised complex I-linked respiration. It is likely that phosgene damages mitochondria through MnSOD and complex I, which contributes to its toxicity. This work uses Drosophila melanogaster for the first time in phosgene research. |
| Chen, H. Y., Wu, P. S., Li, Z. Y., Liu, Y. C., Yeh, S. R., Duan, B. C., Cheng, K. W., Hsu, C. C., Chiu, Y. L., Lee, W. T., Fan, S. Z., Wang, P. Y. (2025). Gut microbiome and host TOR pathway interact to regulate predator-induced aversive memory in Drosophila melanogaster. Proc Natl Acad Sci U S A, 122(25):e2422928122 PubMed ID: 40540603
Summary: The gut microbiome has emerged as a key factor influencing a wide range of host physiological processes and behaviors, though the mechanisms behind these effects remain only partially understood. This study explored the role of the gut microbiome in memory regulation using a parasitoid wasp-induced oviposition depression paradigm in Drosophila melanogaster. These findings show that flies with depleted gut microbiota, either through axenic culture or antibiotic treatment, exhibited significant memory impairments. However, reintroducing the commensal bacterium Lactobacillus plantarum alone was sufficient to restore memory, while coinoculation with Acetobacter pomorum further enhanced memory performance. Hemolymph metabolomic analyses revealed reduced amino acid levels in antibiotic-treated flies, which were linked to impaired Drosophila target of rapamycin (dTOR) signaling. Additionally, genetic manipulation of dTOR or dietary supplementation with branched-chain amino acids either mimicked or rescued the memory deficits caused by antibiotic treatments. These results suggest that the gut microbiome is essential for regulating memory function by maintaining amino acid homeostasis and proper dTOR signaling, with profound implications for advancing knowledge of cognitive regulation. | Yoshino, J., Chiu, A., Morita, T., Yin, C., Tenedini, F. M., Sokabe, T., Emoto, K., Parrish, J. Z. (2025). Heat-off responses of epidermal cells sensitize Drosophila larvae to noxious inputs. bioRxiv, PubMed ID: 40501750
Summary: Perception of external thermal stimuli is critical to animal survival, and although an animal's skin is the largest contact surface for thermal inputs, contributions of skin cells to noxious temperature sensing have not been extensively explored. This study showed that exposure to heat transiently sensitizes Drosophila larvae to subsequent noxious stimuli. This sensitization is induced by prior stimulation of epidermal cells but not nociceptors, suggesting that epidermal cells modulate nociceptor function in response to heat exposure. Indeed, this study found that Drosophila epidermal cells are intrinsically thermosensitive, exhibiting robust heat-off responses following warming to noxious temperatures as well as responses to cooling below comfortable temperatures. Further, epidermal heat-off calcium responses were found to involve influx of extracellular calcium and require the store-operated calcium channel Orai and its activator Stim. Finally, epidermal heat-off responses and heat-evoked nociceptive sensitization exhibit similar temperature dependencies, and Stim and Orai were found to be required in epidermal cells for heat-evoked nociceptive sensitization. Hence, epidermal thermosensory responses provide a form of adaptive sensitization to facilitate noxious heat avoidance. |
| Vega-Cuesta, P., Pulido, D., Abia, D., Herrera, S., Lopez-Varea, A., Ruiz-Gomez, A., Fernandez-Freire, P., Peropadre, A., de Celis, J. F. (2025). A Drosophila ecdysone-deficient model to assess the endocrine disruptor activity of Bisphenol A. Ecotoxicol Environ Saf, 300:118483 PubMed ID: 40499484
Summary: Bisphenol A (BPA) is a well characterized endocrine disruptor that interferes with the activity of a variety of nuclear receptors. For this reason, BPA has the potential to impact the function of the endocrine system and alter cellular physiology. This study presents a novel experimental system to characterize the actions of dietary BPA on organism physiology. Drosophila melanogaster larvae were used that were genetically deficient for the synthesis of the major insect steroid hormone, ecdysone. These larvae exhibit a variety of phenotypes that can be rescued by dietary supplementation of 20-hydroxy-ecdysone or Ponasterone A, a naturally occurring ecdysteroid. The effect of different concentrations of BPA exposure in this genetic background was tested, and this chemical was found to partially rescue the deficit in ecdysone. Furthermore, through in silico structural predictions of the Ecdysone receptor's ligand binding domain, a protein domain was discovered capable of accommodating with different affinities ecdysone, Ponasterone A and BPA molecules. These findings pave the way for novel experimental approaches to identify and characterize new potential vertebrate endocrine disruptors. | Burgmer, S., Meyer Zu Altenschildesche, F. L., Gyenis, A., Lee, H. J., Vilchez, D., Giavalisco, P., Fichant, A., Uhlirova, M., Storelli, G. (2025). Endosymbiont control through non-canonical immune signaling and gut metabolic remodeling. Cell Rep, 44(6):115811 PubMed ID: 40483691
Summary: Animals coexist with bacteria and need to keep these microorganisms under tight control. To achieve such control, pattern recognition receptors (PRRs) sense bacterial cues and induce the production of antimicrobials. This study uncovered a metabolic arm in the control of symbionts by PRRs. In Drosophila, the PRRs PGRP-LC and PGRP-LE were shown to act independently of canonical NF-kappaB signaling to repress essential metabolic functions in the gut, such as digestion and central carbon metabolism. This metabolic switch affects commensal populations and drastically reduces intestinal and systemic populations of the intracellular parasite Wolbachia. Intestinal metabolic remodeling is proposed to complement immune responses by imposing nutrient restriction on intracellular bacteria, whose lifestyle protects them from antimicrobials. These findings reveal a role for PRRs in bacterial control beyond canonical immune pathways and provide insights into how microbial signals modulate symbiotic populations but also nutrition and metabolism in animals. |
Wednesday October 1st - RNAs and Transposons |
| Kolesnikova, T. D., Veselova, O. V., Pokholkova, G. V., Schubert, V., Klenov, M. S. (2025). Localization of rDNA-associated retrotransposons refines the heterochromatin map of the X chromosome in Drosophila melanogaster. Cytogenet Genome Res:1-20 PubMed ID: 40505636
Summary: R1 and R2 retrotransposons specifically integrate into 28S rRNA genes, thereby disrupting many rDNA units within the nucleolar organizer region (NOR) of Drosophila. However, they also appear to play mutualistic roles, contributing to the maintenance of rDNA copy number and the regulation of nucleolar dominance. In addition to their presence in nucleolar rDNA, R1 elements are strongly enriched in the pericentromeric heterochromatin of the X chromosome, located distal to the NOR. This enrichment coincides with several enigmatic genetic phenomena-such as the ABO and cr phenotypes-whose molecular basis remains poorly understood. Notably, this region is one of the least characterized domains of the D. melanogaster genome, lying outside the reference assembly and unresolved in metaphase chromosome preparations. This study performed cytological mapping of R1 and R2 retrotransposons in D. melanogaster heterochromatin using polytene chromosomes from Rif11 mutant, which suppresses under-replication of all types of heterochromatic sequences. These were combined with classical eu-heterochromatic inversions of the X chromosome. Distinct clusters were identified of both R1 and R2 elements within the X chromosome heterochromatin outside the NOR. R1 elements are highly enriched in the region between the heterochromatic Stellate</a> (hSte) gene cluster and the NOR. This zone exhibits a unique response to Su(var)3-9 mutations, characterized by pronounced decondensation and the formation of a pseudo-puff. Proximal to the R1-enriched domain and adjacent to hSte cluster, a region was observed enriched in R2 elements. The edges of the NOR also show R2 enrichment, likely corresponding to intra-nucleolar domains that accumulate transcriptionally inactive rDNA units. In contrast, nucleolar R1 elements-which also mark inactive rDNA units-are more evenly distributed across the entire NOR. Based on these findings, a refined cytological map is proposed of X chromosome heterochromatin in D. melanogaster. | Pandey, S., Nguyen, A. T., Maricle, A. K., DiMario, P. J. (2025). Genetic Factors Linking Nucleolar Stress with R2 Retrotransposon Expression in Drosophila melanogaster. Int J Mol Sci, 26(12) PubMed ID: 40564944
Summary: R2 retrotransposons reside exclusively within the 28S regions of 10-20% of all rDNA genes comprising the nucleolar organizer loci on the X and Y chromosomes of Drosophila melanogaster. These R2-inserted genes are normally silent and heterochromatic. When expressed, however, the R2 transcript is co-transcribed with the 28S rRNA. Self-cleavage releases a 3.6 kb mature R2 transcript that encodes a single protein with endonuclease and reverse transcriptase activities that facilitate R2 element transposition by target-primed reverse transcription. While the molecular details of R2 transposition are known, little is known about the genetic mechanisms that initiate R2 transcription. This study examined R2 expression in wild type versus mutant backgrounds. R2 expression in stage 1-4 wild type egg chambers was variable depending on the stock. R2 expression was silent in wild type stages 5-10 but was consistently active during nurse cell nuclear breakdown in stages 12-13 regardless of the genetic background. Massive R2 expression occurred in stages 5-10 upon loss of Udd, an RNA Pol I transcription factor. Similarly, loss of Nopp140, an early ribosome assembly factor, induced R2 expression more so in somatic tissues. Interestingly, over-expression of the Nopp140-RGG isoform but not the Nopp140-True isoform induced R2 expression in larval somatic tissues, suggesting Nopp140-RGG could potentially affect rDNA chromatin structure. Conversely, Minute mutations in genes encoding ribosomal proteins had minor positive effects on R2 expression. It is concluded that R2 expression is largely controlled by factors regulating RNA Pol I transcription and early ribosome assembly. |
| Rubanova, N., Singh, D., Barolle, L., Chalvet, F., Netter, S., Poidevin, M., Servant, N., Bardin, A. J., Siudeja, K. (2025). An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility. Nucleic Acids Res, 53(11) PubMed ID: 40521665
Summary: Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms, occupy large portions of 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. While it is well characterized that retrotransposon sequences may provide cis-regulatory elements for neighboring genes, how their own expression and mobility are achieved is not well understood. Using long-read DNA sequencing, this study characterized somatic retrotransposition in the Drosophila intestine. Retroelement mobility does not change significantly upon aging and is limited to very few active sub-families. Importantly, a donor locus was identified of an endogenous LTR (long terminal repeat) retroviral element rover, active in the intestinal tissue. Gut activity of the rover donor copy was found to depend on its genomic environment. Without affecting local gene expression, the copy co-opts its upstream genomic sequence, rich in transcription factor binding sites, for somatic expression. Further, it was shown that escargot, a snail-type transcription factor, 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. | Padma, R., Subramanian, M., Chimata, A. V., Rai, A., Yogi, S., Sangeeth, A., Kango-Singh, M., Singh, A. (2025). miR-137 targets Myc to regulate growth during eye development. Development, PubMed ID: 40554764
Summary: During development, regulation of gene-expression is key to cellular homeostasis. Gene-expression regulation by non-coding RNAs (ncRNA) involves prevention of mRNAs accumulation or block translation of their target gene. In a forward genetic-screen to identify the microRNA (miRNA) involved in the growth and patterning of Drosophila eye, a highly conserved miR-137 was discovered. Gain-of-function of miR-137 results in reduced-eye phenotype by downregulating retinal determination and differentiation markers, and by upregulating negative regulators of eye development like Wingless (Wg) and Homothorax (Hth). Loss-of-function of miR-137 results in an enlarged-eye phenotype. Using bioinformatics- and genetic- approaches, oncogene Myc was identified as the target of miR-137. Gain-of-function of Myc can rescue the reduced-eye phenotype of miR-137 gain-of-function or vice-versa. The role of miR-137 in regulating Myc levels in RasV12;scribRNAi, a tumor model of oncogenic cooperation that results in neoplastic tumors. Gain-of-function of miR-137 in RasV12;scribRNAibackground significantly reduced tumor phenotype as well as Myc levels in the eye. These studies highlight miR-137 as a new posttranscriptional regulator of Myc and a promising therapeutic target for diseases associated with Myc-accumulation. |
| Pianezza, R., Scarpa, A., Haider, A., Signor, S., Kofler, R. (2025). Spatiotemporal Tracking of Three Novel Transposable Element Invasions in Drosophila melanogaster over the Last 30 Years. Mol Biol Evol, 42(7) PubMed ID: 40479505
Summary: Transposable elements (TEs) are repetitive sequences capable of mobilizing within genomes, exerting a significant influence on evolution throughout the tree of life. Using a novel approach that does not require prior knowledge of the sequence of repeats, this study identified three novel TE invasions in Drosophila melanogaster: McLE spread between 1990-2000, Souslik between 2009-2012, and Transib1 between 2013-2016. Previous findings were recapitulated, revealing that a total of 11 TEs invaded D. melanogaster over the past two centuries. These 11 invasions increased the fly genome by ∼1 Mbp. Using data from over 1,400 arthropod genomes, Evidence ia provided that these TE invasions were triggered by horizontal transfers, with Drosophila simulans and species of the Drosophila willistoni group acting as putative donors. Through the analysis of ∼600 short-read datasets spanning diverse geographic regions, the rapidity of TE invasions was revealed: Transib1 swiftly multiplied from three isolated epicenters in 2014 to all investigated populations in just 2 years. These findings suggest that anthropogenic activities, which facilitate the range and population expansions of D. melanogaster, could have accelerated the rate of horizontal transposon transfer as well as the spread of the TEs into the worldwide population. Given the significant impact of TEs on evolution and the potential involvement of humans in their dispersal, this research has crucial implications for both evolution and ecology. | Shen, D., Xu, Y., Shi, Q., Li, C., Meng, Z., Wen, Q., Wang, C., Dou, K. (2025). Retrotransposon 3S18 forms self-protective aggregates and prolongs mid-oogenesis. Cell Rep, 44(7):115914 PubMed ID: 40560732
Summary: Transposons are prevalent across nearly all species due to their capacity to mobilize in the host genome. However, their products may begin to affect the host before integration occurs. This study identified that the activation of transposons results in significantly smaller mid-stage oocytes and prolonged mid-oogenesis of Drosophila. Notably, one specific long terminal repeat (LTR) retrotransposon, 3S18, primarily contributes to this phenotype. 3S18 mRNA and its integrase were found to form micrometer-scaled ribonucleoprotein aggregates at cell-cell bridges during these stages. Interestingly, mutants that suppress the formation of these RNP aggregates substantially reduce 3S18 mRNA levels, suggesting that 3S18 aggregates serve functional importance in protecting the retrotransposon products. Live imaging reveals that the accumulation of 3S18 RNP aggregates obstructs host material transportation, resulting in prolonged mid-oogenesis. Finally, forcefully extending oogenesis significantly enhances 3S18 propagation. This study highlights the unique characteristics of 3S18 and its impact on host development. It may shed light on studies of other parasitic elements, including viruses. |
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