Fly最新文献

Drosophila melanogaster is a highly versatile model organism that has profoundly advanced our understanding of human diseases. With more than 60% of its genes having human homologs, Drosophila provides an invaluable system for modelling a wide range of pathologies, including neurodegenerative disorders, cancer, metabolic diseases, as well as cardiac and muscular conditions. This review highlights key developments in utilizing Drosophila for disease modelling, emphasizing the genetic tools that have transformed research in this field. Technologies such as the GAL4/UAS system, RNA interference (RNAi) and CRISPR-Cas9 have enabled precise genetic manipulation, with CRISPR-Cas9 allowing for the introduction of human disease mutations into orthologous Drosophila genes. These approaches have yielded critical insights into disease mechanisms, identified novel therapeutic targets and facilitated both drug screening and toxicological studies. Articles were selected based on their relevance, impact and contribution to the field, with a particular focus on studies offering innovative perspectives on disease mechanisms or therapeutic strategies. Our findings emphasize the central role of Drosophila in studying complex human diseases, underscoring its genetic similarities to humans and its effectiveness in modelling conditions such as Alzheimer's disease, Parkinson's disease and cancer. This review reaffirms Drosophila's critical role as a model organism, highlighting its potential to drive future research and therapeutic advancements.

The aim of the present study was to assess sleep timing in Drosophila melanogaster at different ages, within the setting of an enforced schedule of varying light-dark stimuli, simulating light exposure variations between four typical office working days and one free day spent outside by a human, for a total of 30 days. Locomotor activity recording started when male flies were 3 days old. Flies exhibited a bimodal activity pattern, with a morning and an evening peak, and clear anticipation of the lights on and lights off transitions. From experimental day 10 (i.e. 12-day-old flies) onwards, a decrease in activity counts/increase in sleep amount were observed. On free days, a rise in activity counts and a reduction in sleep amount during the lights on interval was observed and was also present, albeit less obvious, on the subsequent working day during the lights off interval. A progressive delay in sleep onset was observed in the first days of the experiment, peaking on day 4 (i.e. 6-day-old flies), after which sleep onset timing gradually advanced. A delay in sleep offset was also observed for the first 13 days of the experiment, after which sleep offset stabilized. In conclusion, 'adolescent' flies exhibited changes in sleep timing that were reminiscent of those of human adolescents.

The bipartite GAL4/UAS system is the most widely used method for targeted gene expression in Drosophila melanogaster and facilitates rapid in vivo genetic experimentation. Defining precise gene expression patterns for tissues and/or cell types under GAL4 control will continue to evolve to suit experimental needs. However, the precise spatial and temporal expression patterns for some commonly used muscle tissue promoters are still unclear. This missing information limits the precise timing of experiments during development. Here, we focus on three muscle-enriched GAL4 drivers (Mef2-GAL4, C57-GAL4 and G7-GAL4) to better inform selection of the most appropriate muscle promoter for experimental needs. Specifically, C57-GAL4 and G7-GAL4 turn on in the first or second instar larval stages, respectively, and can be used to bypass myogenesis for studies of muscle function after development.

Two of the most important environmental factors that affect the sperm competitive ability in males are the availability of resources and the socio-sexual environment. Numerous studies have investigated the individual effects of these factors, but their combined effect on the evolution of sperm competitive ability remains untested. A crowded larval environment is unique because it simultaneously affects the fitness of the organism through both resource availability and the socio-sexual environment. In this study, we used a set of four laboratory populations of D. melanogaster, evolved under a crowded larval environment for more than 165 generations and their respective controls to investigate how the sperm competitive ability of the males is affected by a single generation of larval crowding versus evolution under a crowded larval environment for more than 165 generations. Our results show that larval crowding negatively affects the sperm defence ability of males evolved in a crowded larval environment, while it has no effect on the sperm defence ability of control males. Additionally, larval crowding negatively impacts the sperm offence ability in both control and evolved populations. Males from populations adapted to a crowded larval environment exhibit lower sperm offence ability at an older age compared to control populations.

Proper formation and specification of Primordial Germ Cells (PGCs) is of special significance as they gradually transform into Germline Stem Cells (GSCs) that are ultimately responsible for generating the gametes. Intriguingly, not only the PGCs constitute the only immortal cell type but several specific determinants also underlying PGC specification such as Vasa, Nanos and Germ-cell-less are conserved through evolution. In Drosophila melanogaster, PGC formation and specification depends on two independent factors, the maternally deposited specialized cytoplasm (or germ plasm) enriched in germline determinants, and the mechanisms that execute the even partitioning of these determinants between the daughter cells. Prior work has shown that Oskar protein is necessary and sufficient to assemble the functional germ plasm, whereas centrosomes associated with the nuclei that invade the germ plasm are responsible for its equitable distribution. Our recent data suggests that Caspar, the Drosophila orthologue of human Fas-associated factor-1 (FAF1) is a novel regulator that modulates both mechanisms that underlie the determination of PGC fate. Consistently, early blastoderm embryos derived from females compromised for caspar display reduced levels of Oskar and defective centrosomes.

Drosophila pseudoobscura and D. persimilis are a sister species pair that have been used as a model for studies of reproductive isolation and speciation for almost 100 years owing to their close evolutionary history, well characterized genetic differences, and overlapping geographic distribution. There are extensive analyses of both pre- and post-zygotic isolation, including studies of courtship divergence, conspecific sperm precedence (CSP) and how reinforcement by natural selection may or may not act to strengthen isolation in sympatry. Post-zygotic analyses explore the underlying mechanics of reproductive isolation; how inversions may give rise to initial speciation events and misexpression of key genes typically found within inversion regions render hybrid offspring unfit or inviable. We aim here to present a history of studies of reproductive isolation between this species pair, looking at how the field has developed over the last century and identifying the open questions and gaps within the literature.

The in situ hybridization chain reaction (isHCR) is a powerful method for visualizing mRNA in many species. We present a rapid isHCR method for Drosophila embryos and ovaries. Ethylene carbonate was added to the hybridization buffer to facilitate the hybridization reaction, and a modified short hairpin DNA was used in the amplification reaction; these modifications decreased the RNA staining time from 3 days to 1 day. This method is compatible with immunohistochemistry and can detect multiple mRNAs. The proposed method could significantly reduce staining time for Drosophila researchers using isHCR.

The drugs mifepristone and rapamycin were compared for their relative ability to increase the life span of mated female Drosophila melanogaster. Titration of rapamycin indicated an optimal concentration of approximately 50 μM, which increased median life span here by average +81%. Meta-analysis of previous mifepristone titrations indicated an optimal concentration of approximately 466 μM, which increased median life span here by average +114%. Combining mifepristone with various concentrations of rapamycin did not produce further increases in life span, and instead reduced life span relative to either drug alone. Assay of maximum midgut diameter indicated that rapamycin was equally efficacious as mifepristone in reducing mating-induced midgut hypertrophy. The mito-QC mitophagy reporter is a previously described green fluorescent protein (GFP)-mCherry fusion protein targeted to the outer mitochondrial membrane. Inhibition of GFP fluorescence by the acidic environment of the autophagolysosome yields an increased red/green fluorescence ratio indicative of increased mitophagy. Creation of a multi-copy mito-QC reporter strain facilitated assay in live adult flies, as well as in dissected midgut tissue. Mifepristone was equally efficacious as rapamycin in activating the mito-QC mitophagy reporter in the adult female fat-body and midgut. The data suggest that mifepristone and rapamycin act through a common pathway to increase mated female Drosophila life span, and implicate increased mitophagy and decreased midgut hypertrophy in that pathway.

Talaromycosis, caused by Talaromyces marneffei (T. marneffei, formerly known as Penicillium marneffei), is an opportunistic invasive mycosis endemic in tropical and subtropical areas of Asia with high mortality rate. Despite various infection models established to study the immunological interaction between T. marneffei and the host, the pathogenicity of this fungus is not yet fully understood. So far, Drosophila melanogaster, a well-established genetic model organism to study innate immunity, has not been used in related research on T. marneffei. In this study, we provide the initial characterization of a systemic infection model of T. marneffei in the D. melanogaster host. Survival curves and fungal loads were tested as well as Toll pathway activation was quantified by RT-qPCR of several antimicrobial peptide (AMP) genes including Drosomycin, Metchnikowin, and Bomanin Short 1. We discovered that whereas most wild-type flies were able to overcome the infection, MyD88 or Toll mutant flies failed to prevent fungal dissemination and proliferation and ultimately succumbed to this challenge. Unexpectedly, the induction of classical Toll pathway activation readouts, Drosomycin and Bomanin Short 1, by live or killed T. marneffei was quite limited in wild-type flies, suggesting that the fungus largely escapes detection by the systemic immune system. This unusual situation of a poor systemic activation of the Toll pathway and a strong susceptibility phenotype of MyD88/Toll might be accounted for by a requirement for this host defence in only specific tissues, a hypothesis that remains to be rigorously tested.