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Current papers in developmental biology and gene function
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July 2026 June 2026 May 2026 April 2026 March 2026 February 2026 January 2026 December 2025 November 2025 October 2025 September 2025 August2025 July 2025 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 December 2023 December 2022 December 2021 December 2020 December 2019 | Vrdoljak, J., Soto, I. M., Carreira, V. P., Padro, J. (2025). Environmental stress differentially affects phenotypic modularity and fluctuating asymmetry in generalist and specialist cactophilic Drosophila. Journal of evolutionary biology, 38(3):404-416 PubMed ID: 39821346
Summary: Modularity and developmental (in)stability have the potential to influence phenotype production and, consequently, the evolutionary trajectories of species. Depending on the environmental factors involved and the buffering capacity of an organism, different developmental outcomes are expected. Cactophilic Drosophila species provide an established eco-evolutionary model with well-studied ecological conditions, making them ideal for studying these phenomena. This study investigated how variations in larval diet and exposure to alkaloids on primary and secondary host plants affect the degree of integration/modularity and fluctuating asymmetry (FA, a proxy for developmental instability) of wing shape in two sibling species with different degrees of specialisation: Drosophila buzzatii (generalist) and Drosophila koepferae (specialist). Additionally, the anterior-posterior modular configuration was compared with a recently proposed proximal-distal modular configuration. The results revealed greater independence among proximal-distal modules compared to anterior-posterior modules. Moreover, sex-specific responses were observed, with males exhibiting greater susceptibility to stressful environments than females. Each species showed a particular trait pattern across treatments: D. buzzatii showed increased integration and FA when reared in a nutrient-poor, alkaloid-rich secondary host, while D. koepferae displayed similar responses in novel environments characterised by double doses of alkaloids on the secondary host plant. These findings align with the generalist-specialist paradigm, suggesting that specialists may be challenged by novel environments, whereas generalists may be more affected by stressful conditions. This study highlights the importance of considering each part of the proximal-distal wing axis independently, and the need to consider ecological-evolutionary history when investigating the relationship between complex phenotypic traits and environmental stress. | Torres-Oliva, M., Buchberger, E., Buffry, A. D., Kittelmann, M., Guerrero, G., Sumner-Rooney, L., Gaspar, P., Bullinger, G. C., Jimenez, J. F., Casares, F., Arif, S., Posnien, N., Nunes, M. D. S., McGregor, A. P., Almudi, I. (2025). Heterochrony in orthodenticle expression is associated with ommatidial size variation between Drosophila species. BMC biology, 23(1):34 PubMed ID: 39901145
Summary: The compound of insects exhibit extensive variation in ommatidia number and size, which affects how they see and underlies adaptations in their vision to different environments and lifestyles. However, very little is known about the genetic and developmental bases of differences in eye size. Previous work showed that the larger eyes of Drosophila mauritiana compared to D. simulans are generally caused by differences in ommatidia size rather than number. Furthermore, an X-linked chromosomal region was identified in D. mauritiana that results in larger eyes when introgressed into D. simulans. This study used a combination of fine-scale mapping and gene expression analysis to further investigate positional candidate genes on the X chromosome. Earlier expression of orthodenticle (otd) during ommatidial maturation in D. mauritiana than in D. simulans, and this gene was shown to be required for the correct organisation and size of ommatidia in D. melanogaster. The activity of an otd eye enhancer was found to be consistent with the difference in the expression of this gene between species, with the D. mauritiana enhancer sequence driving earlier expression than that of D. simulans. When otd expression is driven prematurely during D. melanogaster eye development, the ommatidia grow larger, supporting a possible role for the timing of otd expression in regulating ommatidial size. Potential direct targets of Otd were identified that are differentially expressed between D. mauritiana and D. simulans during ommatidial maturation. Taken together, these results suggest that differential timing of otd expression may contribute to natural variation in ommatidia size between D. mauritiana and D. simulans, providing new insights into the mechanisms underlying the regulation and evolution of compound eye size in insects. |
| Keaney, T. A., Holman, L. (2025). Quantifying the phenome-cwide response to sex-specific selection in Drosophila melanogaster. Evolution; international journal of organic evolution, 79(5):765-778 PubMed ID: 39918910
Summary: In species with separate sexes, the selection on males causes evolutionary change in female traits values (and vice versa) via genetic correlations, which has far-reaching consequences for adaptation. This study utilized a sex-specific form of Robertson's Secondary Theorem of Natural Selection to estimate the expected response to selection for 474 organismal-level traits and ~28,000 gene expression traits measured in the Drosophila Genetic Reference Panel (DGRP). Across organismal-level traits, selection acting on males produced a larger predicted evolutionary response than did selection acting on females, even for female traits; while for transcriptome traits selection on each sex produced a roughly equal average evolutionary response. For most traits, the selection on males and females was predicted to move average trait values in the same direction, though for some traits, the selection on one sex increased trait values while the selection on the other sex decreased them, implying intralocus sexual conflict. These results provide support for the hypothesis that males experience stronger selection than females, potentially accelerating adaptation in females. Furthermore, sex-opposite responses to selection appear to exist for only a small proportion of traits, consistent with observations that the intersex genetic correlation for fitness is positive but less than one in most populations so far studied. | Mermet, J., Cruchet, S., Borbora, A. S., Lee, D., Chai, P. C., Jang, A., Menuz, K., Benton, R. (2025). Multilayer regulation underlies the functional precision and evolvability of the olfactory system. bioRxiv, PubMed ID: 39868256
Summary: Sensory neurons must be reproducibly specified to permit accurate neural representation of external signals but also able to change during evolution. We studied this paradox in the Drosophila olfactory system by establishing a single-cell transcriptomic atlas of all developing antennal sensory lineages, including latent neural populations that normally undergo programmed cell death (PCD). This atlas reveals that transcriptional control is robust, but imperfect, in defining selective sensory receptor expression. A second layer of precision is afforded by the intersection of expression of functionally-interacting receptor subunits. A third layer is defined by stereotyped PCD patterning, which masks promiscuous receptor expression in neurons fated to die and removes "empty" neurons lacking receptors. Like receptor choice, PCD is under lineage-specific transcriptional control; promiscuity in this regulation leads to previously-unappreciated heterogeneity in neuronal numbers. Thus functional precision in the mature olfactory system belies developmental noise that might facilitate the evolution of sensory pathways. |
| Chang, C. H., de la Cruz, A. F., Natividad, I. M., Noyola, A., Malik, H. S. (2025). Rapid protamine evolution suppresses meiotic drive in Drosophila. bioRxiv, PubMed ID: 40950199
Summary: Many animal species replace histones with protamines during spermatogenesis. Despite their importance for sperm function, protamines rapidly evolve in many species; the biological causes behind their rapid evolution remain unknown. Using in vivo gene replacement, this study investigated the causes and consequences underlying the rapid evolution ofd protamine Mst77F, which is essential for male fertility in D. melanogaster. Mst77F ortholog replacements led to defects in DNA compaction of X-chromosome-bearing sperm compared to Y-chromosome-bearing sperm during spermatogenesis, resulting in fewer X-bearing mature sperm and male-biased progeny. Unlike D. melanogaster, Mst77F is not essential for male fertility in D. yakuba but is still required to suppress sex-ratio distortion. These results suggest that relentless pressure to suppress sex chromosomal meiotic drive drives the rapid evolution of protamines. | Udroiu, I., Sgura, A. (2025). Drosophila telomeric protein Verrocchio is an ortholog of STN1.Genetica, 153(1):11 PubMed ID: 39841234
Summary: In most Eukaryota, telomeres are protected by the CST complex, composed of CTC1, STN1 and TEN1. In Drosophila, instead, another complex is present, composed of Modigliani, Tea and Verrocchio. This study performed a search for STN1 orthologs in Arthropoda, in order to verify if Verrocchio can be considered as such. STN1 in Arthropoda was found to be shorter than in other Metazoa and shares the same architecture with Verrocchio. Despite high sequence divergence between human and Drosophila, this study has discovered that Verrocchio is an ortholog of STN1. |
Monday August 11th - Chromatin |
| Weisz-Hubshman, M., Burrage, L. C., Jangam, S. V., Rosenfeld, J. A., von Hardenberg, S., Bergmann, A., Richter, M. F., Rydzanicz, M., Ploski, R., Stembalska, A., Chung, W. K., Hernan, R. R., Lim, F. Y., Brunet, T., Syrbe, S., Keren, B., Heide, S., Murdock, D. R., Dai, H., Xia, F., Ketkar, S., Dawson, B., Narayanan, V., Graves, H. K., Wangler, M. F., Bacino, C., Lee, B. (2025). De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies. Genet Med, 27(4):101369 PubMed ID: 39891528
Summary: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear. Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies. Seven individuals are described with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. All single-nucleotide variants in RYBP localize to the N-terminal domain of the gene, which encodes the zinc-finger domain and ubiquitin-binding moiety. In vitro studies have demonstrated that the RYBP c.132C>G p.(Cys44Trp) variant causes reduced protein expression but does not affect the binding of YY1, RING1B, or ubiquitin. In vivo overexpression studies in Drosophila melanogaster showed a dramatic functional difference between human RYBP and its variant forms, affecting the C44 amino acid residue. DNA methylation studies suggested a possible episignature associated with RYBP-related disorder. It is concluded that heterozygous de novo variants in RYBP are associated with an identifiable syndromic neurodevelopmental disorder with multiple congenital anomalies. | Chavan, A., Skrutl, L., Uliana, F., Pfister, M., Brandle, F., Tirian, L., Baptista, D., Handler, D., Burke, D., Sintsova, A., Beltrao, P., Brennecke, J., Jagannathan, M. (2025). Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression. PLoS biology, 23(1):e3002984 PubMed ID: 39813297
Summary: Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized. This study used 2 satellite DNA-binding proteins, D1 and Prod, as baits to characterize the chromocenter-associated proteome in Drosophila embryos, ovaries, and testes through quantitative mass spectrometry. D1- and Prod-associated proteins, including known heterochromatin proteins as well as proteins previously unlinked to satellite DNA or chromocenters were identified, thereby laying the foundation for a comprehensive understanding of cellular functions enabled by satellite DNA repeats and their associated proteins. Interestingly, multiple components of the transposon-silencing piRNA pathway were found to be associated with D1 and Prod in embryos. Using genetics, transcriptomics, and small RNA profiling, flies lacking D1 during embryogenesis were found to exhibit transposon expression and gonadal atrophy as adults. This gonadal atrophy can be rescued by mutating the checkpoint kinase, Chk2, which mediates germ cell arrest in response to transposon mobilization. Thus, this study reveals that a satellite DNA-binding protein functions during embryogenesis to silence transposons, in a manner that is heritable across later stages of development. |
| Zolin, I. A., Georgieva, S. G., Nikolenko, J. V. (2025). Evolutionarily Conserved DHX9/MLE Helicase Is Involved in the Regulation of Its Own mRNA Expression Level in Drosophila melanogaster. Doklady Biochemistry and biophysics, 520(1):1-5 PubMed ID: 39899250
Summary: The MLEmle9 mutation on its own mRNA expression level. It was shown that in addition to the previously described deletion in the catalytic domain of the protein, which impairs its helicase activity, the mle9 mutation contains an additional small deletion in the C-terminal domain. In the mle9 mutation background, there was a threefold increase in the expression of the main transcript of the mle gene encoding the full-length protein. Binding of MLE to chromatin at the coding region and promoters of the mle gene and nearby enhancers was analyzed. To exclude the influence of dosage compensation, experiments were performed on females. The data obtained indicate the role of MLE in specific regulation of its own mRNA expression level in vivo at the adult stage. | Liu, W., Deng, L., Wang, M., ..., Gao, P., Li, P., Yu, Y. (2025). Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation. Mol Cell, 85(5):929-947. PubMed ID: 40015272
Summary: he PIWI-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism of piRNA-guided heterochromatin formation and its relationship to transcriptional termination remains elusive. Through RNA interference screening, this study discovered Pcf11 and PNUTS as essential for piRNA-guided silencing in Drosophila germ line. Enforced tethering of Pcf11 leads to co-transcriptional repression and RNA polymerase II (RNA Pol II) stalling, and both are dependent on an α-helical region of Pcf11 capable of forming condensates. An intrinsically disordered region can substitute for the α-helical region of Pcf11 in its silencing capacity and support animal development, arguing for a causal relationship between phase separation and Pcf11's function. Pcf11 stalls RNA Pol II by preferentially forming condensates with the unphosphorylated Spt5, promoted by the PP1/PNUTS phosphatase during termination. It is proposed that Pcf11/Spt5 condensates control termination by decelerating polymerase elongation, a property exploited by piRNAs to silence transposons and initiate RNA-mediated heterochromatin formation. |
| Segert, J. A., Bulyk, M. L. (2025). Histone H4 lysine 20 monomethylation is not a mark of transcriptional silencers. Doklady Biochemistry and biophysics, 520(1):152-155. bioRxiv, PubMed ID: 39868205
Summary: Transcriptional silencers are cis-regulatory elements that downregulate the expression of target genes. Although thousands of silencers have been identified experimentally, a predictive chromatin signature of silencers has not been found. H4K20me1 previously was reported to be highly enriched among human silencers, but this reanalysis of those data using an appropriate background revealed that the enrichment is only marginal. H4K20me1 ChIP-seq profiles were generated in Drosophila S2 cells, which similarly showed that H4K20me1 does not mark Drosophila silencers and instead is associated with active transcription. Silencers remain a poorly annotated, difficult to predict class of cis-regulatory elements whose specific chromatin features remain to be identified. | Chmykhalo, V. K., Amendola, D., Shidlovskii, Y. V., Lebedeva, L. A., Schedl, P., Giordano, E. (2025). Functional Role of Bap170 Domains in Enhancer-Dependent Gene Activity in Drosophila melanogaster. Doklady Biochemistry and biophysics, 520(1):152-155 PubMed ID: 39899248
Summary: The Bap170 subunit of the SWI/SNF chromatin remodeler exhibits activator functions when artificially recruited to the LacZ reporter promoter in enhancer-dependent transcription. In this study, the functional significance of Bap170 protein domains in reporter activation was analyzed. Deletion of the ARID domain does not reduce Bap170 activity. Increased expression of the LacZ reporter was observed in the form of Bap170 without a region that includes LXXLL motifs. Deletions of the central (RFX domain and IDRs) and C-terminal region (zinc fingers) of Bap170 lead to a significant decrease in transgene expression. Apparently, these regions of Bap170 are critical for the function of this protein in enhancer-dependent transcription. |
Friday August 7th - Disease Models |
| Zhang, S., Wang, L., Yi, S., Tsai, Y. T., Cheng, Y. H., Lin, Y. T., Lin, C. C., Lee, Y. H., Wang, H., Li, S., Wang, R., Liu, Y., Yan, W., Liu, C., He, K. W., Ho, M. S. (2025). Drosophila aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation. Autophagy, 21(5):1039-1058 PubMed ID: 39878136
Summary: Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. This study presents evidence that aux (auxilin), the Drosophila homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn. Whereas SNCA/α-syn accumulates prominently in lysosomes devoid of glial aux, levels of injected SNCA/α-syn preformed fibrils are further enhanced in the absence of microglial GAK. Mechanistically, aux mediates phosphorylation at the serine 543 of Vha44, the V(1) C subunit of the vacuolar-type H(+)-translocating ATPase (V-ATPase), and regulates its assembly to control proper acidification of the lysosomal milieu. Expression of Vha44, but not the Vha44 variant lacking S543 phosphorylation, restores lysosome acidity, locomotor deficits, and DA neurodegeneration upon glial aux depletion, linking this pathway to PD. These findings identify a phosphorylation-dependent switch controlling V-ATPase assembly for lysosomal SNCA/α-syn degradation in glia. Targeting the clearance of glial SNCA/α-syn inclusions via this lysosomal pathway could potentially be a therapeutic approach to ameliorate the disease progression in PD. | Yu, G., Chen, K., Yang, M., Wu, Q. (2025). Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females. Aging cell, 24(6):e70011 PubMed ID: 39920895
Summary: The trade-off between reproduction and lifespan has been documented across a wide array of organisms, ranging from invertebrates to mammals. In malnourishing dietary conditions, inhibition of the reproductive processes generally extends the lifespan of females. However, the underlying mechanisms through which nutritional competition driven by reproduction accelerates aging remain poorly understood. Using female Drosophila melanogaster as a model, this study showed that among various dietary conditions lacking specific nutrients, only sterol deficiency (especially cholesterol) significantly exacerbated both the incidence and severity of intestinal barrier deterioration during aging. Sterile mutation specifically ameliorated such damage in sterol-deprived diets, but failed to alleviate age-related intestinal barrier deterioration under other nutritional conditions. Additionally, this study demonstrated that the lifespan extension and intestinal barrier amelioration, accompanied by a reproductive suppression effect, through the pharmacological inhibition of mTOR or Ras-Erk signaling using rapamycin or trametinib, were significantly modulated by cholesterol levels. Our study also identifies the morphological changes in excreta as a sensitive biomarker for early intestinal dysfunction. Collectively, these results suggest that the impairment of the intestinal barrier caused by reproductive-induced sterol competition constitutes a significant factor limiting female lifespan in nutritionally unbalanced diets. This work elucidates a salient aspect of the complex interplay between reproductive resource allocation and somatic maintenance, thereby enhancing our understanding of how diet impacts the aging process. |
| Ping, X., Li, Q., Ding, M., Yu, Z., Yi, Q., Li, Y., Gu, W., Zhang, P., Zhang, Z., Zheng, L. (2025). Hypoxic compound exercise improves cardiac function in Drosophila high fructose diet via KHK. J Mol Cell Cardiol, 201:95-104 PubMed ID: 39954938
Summary: Overconsumption of fructose has been linked to the development of systemic metabolic and cardiac diseases, yet few studies have focused on the link between cardiac fructose metabolism and the development of heart disease. Low-oxygen complex exercise is considered an effective means of treating and preventing metabolic diseases and improving cardiac function, however, it is unclear, the link between low-oxygen complex exercise and high-fructose-induced heart disease. Therefore, the aim of this study was to investigate the effect of hypoxic complex exercise on heart disease on a high fructose diet. The results of the study found that hypoxic compound exercise improved the upregulation of inflammatory factor Upd3 and systemic fat accumulation in the heart induced by high fructose diet by inhibiting the expression of KHK gene in the heart; and it improved the impaired cardiac rhythmic function and pumping function, improved the disorder of myofilament fiber arrangement, reduced the level of cardiac oxidative stress, and reduced cardiac collagen deposition. In addition, cardiac KHK-specific knockdown had the same effect on high fructose diet hearts. Compared with single KHK cardiac-specific knockdown or hypoxic combination exercise, hypoxic combination exercise combined with KHK cardiac-specific knockdown was superior in improving the high-fructose diet-induced increase in arrhythmia index, systolic and diastolic dysfunction, and decrease in fractional shortening. Therefore, it is concluded that hypoxic complex exercise improved high-fructose diet-induced cardiac rhythmic function and pumping dysfunction by reducing KHK expression. | Prifti, M. V., Nuga, O., Dulay, R. O., Patel, N. C., Kula, T., Libohova, K., Jackson-Butler, A., Tsou, W. L., Richardson, K., Todi, S. V. (2025). Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease. Neurobiology of disease, 207:106834 PubMed ID: 39921111
Summary: Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disorder that presents with ataxia, dementia and epilepsy. As a member of the polyglutamine family of diseases, DRPLA is caused by abnormal CAG triplet expansion beyond 48 repeats in the protein-coding region of ATROPHIN 1 (ATN1), a transcriptional co-repressor. To better understand DRPLA, new Drosophila lines were generatede that can be induced to express full-length, human ATN1 with a normal (Q7) or pathogenic (Q88) repeat in a variety of cells, including neuronal, glial or any other type of tissue. Expression of ATN1 is toxic, with the polyglutamine-expanded version being consistently more problematic than wild-type ATN1. Fly motility, longevity and internal structures are negatively impacted by pathogenic ATN1. RNA-seq identified altered protein quality control and immune pathways in the presence of pathogenic ATN1. Based on these data, genetic experiments were conducted that confirmed the role of protein quality control components that ameliorate or exacerbate ATN1 toxicity. Hsc70-3, a chaperone, arose as a likely suppressor of toxicity. VCP (a proteasome-related AAA ATPase), Rpn11 (a proteasome-related deubiquitinase) and select DnaJ proteins (co-chaperones) were inconsistently protective, depending on the tissues where they were expressed. Lastly, informed by RNA-seq data that exercise-related genes may also be involved in this model of DRPLA, short-term exercise were conducted, that improved overall fly motility. This new model of DRPLA will prove important to understanding this understudied disease and will help to identify therapeutic targets for it. |
| Tennant, N., Pavuluri, A., O'Connor-Giles, K., Singh, G., Larschan, E., Singh, R. (2025). TimeFlies: an snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging. bioRxiv, PubMed ID: 39896546
Summary: Although multiple high-performing epigenetic aging clocks exist, few are based directly on gene expression. Such transcriptomic aging clocks allow extraction of age-associated genes directly. However, most existing transcriptomic clocks model a subset of genes and are limited in their ability to predict novel biomarkers. With the growing popularity of single-cell sequencing, there is a need for robust single-cell transcriptomic aging clocks. Moreover, clocks have yet to be applied to investigate the elusive phenomenon of sex differences in aging. This study introduces TimeFlies, a pan-cell-type scRNA-seq aging clock for the Drosophila melanogaster head. TimeFlies uses deep learning to classify the donor age of cells based on genome-wide gene expression profiles. Using explainability methods, key marker genes contributing to the classification were identified, with lncRNAs showing up as highly enriched among predicted biomarkers. The top biomarker gene across cell types is lncRNA:roX1, a regulator of X chromosome dosage compensation, a pathway previously identified as a top biomarker of aging in the mouse brain. This finding was validated experimentally, showing a decrease in survival probability in the absence of roX1 in vivo. Furthermore, sex-specific TimeFlies clocks were trained and significant differences were noted in model predictions and explanations between male and female clocks, suggesting that different pathways drive aging in males and females. | Vos, M., Ott, F., Gillo, H., Cesare, G., Misera, S., Busch, H., Klein, C. (2025). Endoplasmic Reticulum Proteins Impact Penetrance in a Pink1-Mutant Drosophila Model. International journal of molecular sciences, 26(3) PubMed ID: 39940747
Summary: Parkinson's disease (PD) is a neurodegenerative disorder with a high variability of age at onset, disease severity, and progression. This suggests that other factors, including genetic, environmental, or biological factors, are at play in PD. The loss of PINK1 causes a recessive form of PD and is typically fully penetrant; however, it features a wide range in disease onset, further supporting the existence of protective factors, endogenous or exogenous, to play a role. The loss of Pink1 in Drosophila melanogaster results in locomotion deficits, also observed in PINK1-related PD in humans. In flies, Pink1 deficiency induces defects in the ability to fly; nonetheless, around ten percent of the mutant flies are still capable of flying, indicating that advantageous factors affecting penetrance also exist in flies. This study aimed to identify the mechanisms underlying this reduced penetrance in Pink1-deficient flies. Genetic screening was performed in pink1-mutant flies to identify RNA expression alterations affecting the flying ability. The most important biological processes involved were transcriptional and translational activities, endoplasmic reticulum (ER) regulation, and flagellated movement and microtubule organization. Two ER-related proteins, zonda and windbeutel, were validated to positively affect the flying ability of Pink1-deficient flies. Thus, the data suggest that these processes are involved in the reduced penetrance and that influencing them may be beneficial for Pink1 deficiency. |
Thursday August 6th - Larval and Adult Neural Structure, Development and Function |
| Leier, H. C., Foden, A. J., Jindal, D. A., Wilkov, A. J., Van der Linden Costello, P., Vanderzalm, P. J., Coutinho-Budd, J., Tabuchi, M., Broihier, H. T. (2025). Glia control experience-dependent plasticity in an olfactory critical period. eLife, 13 PubMed ID: 39883485
Summary: Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The Drosophila antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience. A recent study found that glia shape antennal lobe development in young adults, leading to the question whether glia also drive experience-dependent plasticity during this period. This study defines a critical period for structural and functional plasticity of OSN-PN synapses in the ethyl butyrate (EB)-sensitive glomerulus VM7. EB exposure for the first 2 days post-eclosion drives large-scale reductions in glomerular volume, presynapse number, and post- synaptic activity. Crucially, pruning during the critical period has long-term consequences for circuit function since both OSN-PN synapse number and spontaneous activity of PNs remain persistently decreased following early-life odor exposure. The highly conserved engulfment receptor Draper is required for this critical period plasticity as ensheathing glia upregulate Draper, invade the VM7 glomerulus, and phagocytose OSN presynaptic terminals in response to critical-period EB exposure. Loss of Draper fully suppresses the morphological and physiological consequences of critical period odor exposure, arguing that phagocytic glia engulf intact synaptic terminals. These data demonstrate experience-dependent pruning of synapses and argue that Drosophila olfactory circuitry is a powerful model for defining the function of glia in critical period plasticity. | Stonemetz, J. M., Chantzi, N., Perkins, E. L., Peralta, A. J., Possidente, D. R., Tagariello, J. P., Bennett, M. M., Alnassar, H., Dacks, A. M., Vecsey, C. G. (2025). The Roles of Discrete Populations of Neurons Expressing Short Neuropeptide F in Sleep Induction in Drosophila melanogaster. Genes, brain, and behavior, 24(1):e70010 PubMed ID: 39918815
Summary: Sleep is of vital importance, yet an understanding the neuronal networks that control the amount and timing of sleep is yet to be aschieved. There is substantial conservation of known sleep-regulating transmitters, allowing for studies in simpler organisms to lead the way in gaining insight into the organization of sleep control circuits. In Drosophila melanogaster, recent work showed that optogenetic activation of neurons that produce the neuropeptide Y (NPY)-related transmitter short neuropeptide F (sNPF) increases time spent asleep. However, sNPF is expressed in several neuronal populations, and thus it is unknown which of those populations play roles in the sleep-promoting effect. This study addressed this issue using a genetic approach to limit optogenetic activation to subsets of sNPF-expressing neurons. Sleep promotion was found to be shorter-lived when Cryptochrome (CRY)-positive neurons were excluded from being activated. Pigment-dispersing factor (PDF) neurons were not required for sleep promotion, nor were mushroom body (MB) neurons. Acute reactions to a short, 10-s period of optogenetic activation were largely unchanged by excluding activation of the three neuronal populations mentioned above. Together, these results suggest that clock neurons that are CRY-positive and PDF-negative are important contributors to the long-lasting sleep promotion produced by sNPF neuron activation. However, other neurons targeted by the sNPF-GAL4 driver appear to mediate the more rapid behavioral responses. Future studies will seek to identify these additional sNPF neuron populations and to determine how sNPF-expressing clock neurons act in concert with other neuronal circuits to promote sleep. |
| Nguyen, Q. D., Fujii, K., Ishibashi, K., Hashiba, H., Ohtsubo, W., Kitazawa, H., Tanimoto, H., Fuse, N., Kurata, S. (2025). Regulation of Gut Starvation Responses Through Drosophila NP3253 Neurons. Genes to cells : devoted to molecular & cellular mechanisms, 30(2):e70005 PubMed ID: 39904737
Summary: The "gut-brain axis," a bidirectional communication system between the gastrointestinal tract and the central nervous system, plays a crucial role in regulating complex physiological functions in response to nutrients, pathogens, and microbiota. However, the cellular and molecular mechanisms governing this regulation remain poorly understood. Using Drosophila melanogaster as a model organism, previous work identified NP3253 neurons, located in both the brain and gut, as key contributors to gut homeostasis during oral bacterial infection. This study found a novel role of NP3253 neurons, identified by a driver line used to mark and manipulate a specific subset of roughly 100 enteric neurons in regulating starvation resistance. A subset of NP3253 neurons in the gut were activated during starvation. To investigate downstream effect, RNA-Seq analysis was conducted on the gut of adult flies with genetically silenced NP3253 neurons, comparing gene expression under starved and fed conditions. This analysis identified 26 genes differentially expressed in response to both starvation and NP3253 neuronal activity. Among these, CG12643, encoding an uncharacterized short peptide, was found to be essential for starvation resistance in the gut. These findings demonstrate that NP3253 neurons modulate the gut gene expression in response to starvation, thereby supporting physiological adaptation to environmental stressors. | Raun, N., Jones, S. G., Kerr, O., Keung, C., Butler, E. F., Alka, K., Krupski, J. D., Reid-Taylor, R. A., Ibrahim, V., Williams, M., Top, D., Kramer, J. M. (2025). Trithorax regulates long-term memory in Drosophila through epigenetic maintenance of mushroom body metabolic state and translation capacity. PLoS biology, 23(1):e3003004 PubMed ID: 39869640
Summary: The role of epigenetics and chromatin in the maintenance of postmitotic neuronal cell identities is not well understood. This study shows that the histone methyltransferase Trithorax (Trx) is required in postmitotic memory neurons of the Drosophila mushroom body (MB) to enable their capacity for long-term memory (LTM), but not short-term memory (STM). Using MB-specific RNA-, ChIP-, and ATAC-sequencing, this study found that Trx maintains homeostatic expression of several non-canonical MB-enriched transcripts, including the orphan nuclear receptor Hr51, and the metabolic enzyme lactate dehydrogenase (Ldh). Through these key targets, Trx facilitates a metabolic state characterized by high lactate levels in MBγ neurons. This metabolic state supports a high capacity for protein translation, a process that is essential for LTM, but not STM. These data suggest that Trx, a classic regulator of cell type specification during development, has additional functions in maintaining underappreciated aspects of postmitotic neuron identity, such as metabolic state. This work supports a body of evidence suggesting that a high capacity for energy metabolism is an essential cell identity characteristic for neurons that mediate LTM. |
| Walker, S. R., Pena-Garcia, M., Devineni, A. V. (2025). Connectomic analysis of taste circuits in Drosophila. Scientific reports, 15(1):5278 PubMed ID: 39939650
Summary: A sense of taste is critical for regulating food consumption. The fruit fly Drosophila represents a highly tractable model to investigate mechanisms of taste processing, but taste wcircuits beyond sensory neurons are largely unidentified. This study used a whole-brain connectome to investigate the organization of Drosophila taste circuits. Pathways were traced from four populations of sensory neurons that detect different taste modalities and project to the subesophageal zone (SEZ), the primary taste region of the fly brain. We find that second-order taste neurons are primarily located within the SEZ and largely segregated by taste modality, whereas third-order neurons have more projections outside the SEZ and more overlap between modalities. Taste projections out of the SEZ innervate regions implicated in feeding, olfactory processing, and learning. Interconnections within and between taste pathways were analyzed, modality-dependent differences in taste neuron properties were characterize, other types of inputs onto taste pathways were identified, and computational simulations were used to relate neuronal connectivity to predicted activity. These studies provide insight into the architecture of Drosophila taste circuits. | Nobel, S., Danchin, E., Isabel, G. (2025). Long-term social memory of mate copying in Drosophila melanogaster is localized in mushroom bodies. Scientific reports, 15(1):5262 PubMed ID: 39939402
Summary: Long-term social memory (LTSM) is a key feature to elicit the cultural inheritance of behaviour independently of genetics. However, the neurobiological basis of LTSM remains largely unknown. Pevious studies used the Drosophila animal model, which is known to perform mate copying through observational learning of the mate choice of conspecifics to show that the expression of the rutabaga gene, a calcium/calmodulin-dependent adenylyl cyclase (AC-Rut+) that acts as a coincidence detector enabling associative learning, is necessary and sufficient in the γ-Kenyon cells (KCs) of the mushroom bodies (MBs). This study shows that the expression of AC-Rut(+) in both the γ- and the α/β-KCs is required for LTSM involving de novo protein synthesis in a mate-copying context, whether using demonstrations involving real flies or involving pictures of copulating conspecifics. Thus, pathways of short- and long-term memory show considerable overlap in the MBs across social vs. asocial learning contexts. |
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