Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from cli...Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.展开更多
Drosophila melanogaster has been a popular model organism in the study of sleep and circadian rhythm.The Drosophila activity monitoring(DAM)system is one of the many tools developed for investigating sleep behavior in...Drosophila melanogaster has been a popular model organism in the study of sleep and circadian rhythm.The Drosophila activity monitoring(DAM)system is one of the many tools developed for investigating sleep behavior in fruit flies and has been acknowledged by researchers around the world for its simplicity and cost-effectiveness.Based on the simple activity data collected by the DAM system,a wide range of parameters can be generated for sleep and circadian studies.However,current programs that analyze DAM data cover a limited number of metrics and fail to provide individual data for the user to plot graphs and conduct analysis using other software.Therefore,we have developed SleepyFlyR,an R package that:(1)is simple and easy to use with a user-friendly user interface script;(2)provides a comprehensive analysis of sleep and activity parameters;(3)generates double-plotted graphs for sleep and activity patterns;(4)offers visualization of sleep and activity profiles across multiple days or within a single day;(5)calculates the changes of sleep and activity parameters between baseline and experiment;(6)stores both summary data and individual data in files with unique title.展开更多
Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,wh...Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.展开更多
Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[...Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[1,2].While key elements are characterized[3,4],how a single molecule integrates sleep and memory remains unknown.展开更多
Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying m...Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.展开更多
Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated tha...Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated that Lateolabrax japonicus peptides(LPH),rich in Glu,Gly,and hydrophobic amino acids,exhibited remarkable antioxidant activity in vitro,with though its action mechanism yet to be revealed.Therefore,to assess the in vivo antioxidative properties of LPH,we employed H_(2)O_(2) to generate oxidative stress in Drosophila melanogaster model.Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH’s enhancement of the antioxidant defense system and intestinal functions.Antioxidant effects were manifested by a decrease in malondialdehyde(MDA)levels,elevated superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)activities,decreased levels of reactive oxygen species(ROS)in intestinal epithelial cells,and the preservation of intestinal length.LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells.At the gene level,LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level.Furthermore,high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H_(2)O_(2)-induced Drosophila.These findings provide a deeper understanding of the antioxidative mechanism of LPH,suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.展开更多
It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we p...It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we present an analysis of the evolutionary history of a putative de novo gene,lawc,which overlaps with the conserved Trf2 gene,which encodes a general transcription factor in Drosophila melanogaster.We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region(UTR)of Trf2 and displays an extensive spatiotemporal expression pattern.One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short,highly conserved regions located in Trf2 introns.This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved genes.The observed lawc expression pattern may be due to the overlap of lawc with the 5'-UTR of Trf2.This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.展开更多
General anesthesia(GA)is a pharmacologically induced,reversible state characterized by unconsciousness,amnesia,analgesia,and immobility in response to noxious stimuli.Accumulating evidence from animal models has eluci...General anesthesia(GA)is a pharmacologically induced,reversible state characterized by unconsciousness,amnesia,analgesia,and immobility in response to noxious stimuli.Accumulating evidence from animal models has elucidated diverse mechanisms of the action underlying GA,including disruption of large-scale brain network connectivity,regulation of multiple neural pathways,and modulation of specific receptors and ion channels.Despite advances in dissecting the neurobiological basis of anesthetic action,the precise cellular and circuit-level processes remain incompletely understood,limiting the development of safer and more effective strategies.Recent studies in Drosophila melanogaster,a genetically tractable model organism offering robust genetic analysis,advanced imaging capabilities,and compact neural architecture,have yielded critical insights into the conserved neurobiological mechanisms of GA,offering translational value for mammalian systems.This review outlines:1)experimental paradigms used to evaluate anesthetic sensitivity and behavioral responses in Drosophila;2)molecular targets and their mechanistic roles in mediating GA;and 3)neural circuit architectures and activity patterns shared by GA and sleep.Cross-species comparisons are integrated to highlight conserved mechanisms that may guide the development of more refined anesthetic strategies.展开更多
Neural stem cells(NSCs)play a fundamental role in generating diverse neuronal populations that contribute to the formation of intricate neural circuitry.Disturbances arising from intrinsic or extrinsic factors can alt...Neural stem cells(NSCs)play a fundamental role in generating diverse neuronal populations that contribute to the formation of intricate neural circuitry.Disturbances arising from intrinsic or extrinsic factors can alter the developmental behavior of NSCs and disrupt nervous system homeostasis.While intrinsic regulatory mechanisms have been elucidated extensively in invertebrate or vertebrate models,the regulatory mechanisms underlying extrinsic cues from the cellular environment remain poorly understood.This review synthesized recent research on cellular ambient effects,including the microenvironment,systemic environment and external factors,on NSCs in Drosophila.Key topics include spatial cues,NSC-glia interactions,long-distance regulation by tissues such as the fat body,and the external environmental stressors like irradiation or viral infection.By integrating these findings,this review provides new insights into how extrinsic signals shape NSCs and bridges gaps between foundational research and clinical translation.展开更多
Spinocerebellar ataxia(SCA)type 51 is a neurodegenerative disease caused by CAG repeat expansions in exon 1 of the THAP11 gene.These repeats are translated into a glutamine-rich protein,THAP11-polyQ,which forms protei...Spinocerebellar ataxia(SCA)type 51 is a neurodegenerative disease caused by CAG repeat expansions in exon 1 of the THAP11 gene.These repeats are translated into a glutamine-rich protein,THAP11-polyQ,which forms protein aggregates and exhibits toxicity in cell models;however,the underlying mechanism remains unclear.In this study,we generate transgenic Drosophila models expressing varying lengths of THAP11-polyQ using the UAS-GAL4 system and assess neurodegeneration through pathological and behavioral analyses.Our results demonstrate that expression of THAP11-polyQ in transgenic flies leads to progressive neuronal cell loss,locomotor deficiency,and reduced survival.RNA sequencing of patient-derived skin fibroblasts reveals significant enrichment of the PI3K–Akt–mTOR pathway,and electron microscopy of transgenic flies shows an increase in multilamellar bodies,suggesting involvement of autophagy in SCA51.Consequently,we treat the fly model with rapamycin,an mTOR inhibitor known to enhance autophagy.This treatment reduces toxic THAP11-polyQ protein aggregates,significantly alleviates neuronal degeneration,and improves locomotor function,consistent with the rescue effects observed upon overexpression of Atg8a.Overall,these findings suggest that the Drosophila model,which recapitulates the neurodegenerative features of SCA51,can be used to investigate pathogenic mechanisms and that rapamycin holds promising potential as a therapeutic approach for this disease.展开更多
[ Objective ] The aim of this study was to investigate the infectivity of Nosema bombycis to drosophila, which offered a new vision for systematical studies on the infection mechanism of Nosema bombycis, and also prov...[ Objective ] The aim of this study was to investigate the infectivity of Nosema bombycis to drosophila, which offered a new vision for systematical studies on the infection mechanism of Nosema bombycis, and also provided reference for the bio-control effect of Nosema bombycis. [ Method ] Nosema bombycis was used to feed wild type and mutant drosophila, and the morphological observation of Nosema bombycis in drosophila body fluid was also analyzed by calcofluor white M2R fluorescent staining. [ Result] Nosema bombycis could infect drosophila, and the number of Nosema bombycis in the infected mutant drosophila was higher than that in wild type drosophila. [ Conclusion ] Nosema bombycis can infect drosophila, which provides primary reference for studies on the infectivity of Nosema bombycis to other hosts and also lays a foundation for further study on the infection mechanism of Nosema bombycis.展开更多
Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate ear...Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.展开更多
Spotted wing drosophila, Drosophila suzukii (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are particularly susceptible...Spotted wing drosophila, Drosophila suzukii (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are particularly susceptible to infestation, and fruit producers are desperate for methods to control this pest. One of the keys to developing an integrated management program for SWD is to understand host preference and varietal susceptibility of highly susceptible crop hosts. Working in replicated small plots, experiments were conducted to evaluate differences in varietal susceptibility on cold hardy red primocane fruiting raspberries. Significant differences were observed in both the level of infestation and in the average number of larvae per berry by variety. In addition, it appears that there is a significant negative correlation between the level of infestation and the number of larvae per fruit with the time of sampling, but only an interaction of variety and time for the number of larvae per berry. These data provide a better understanding of the biology and ecology of this pest which is critical in refining current management practices. Knowledge of these interactions can aid in optimizing control strategies such as fine-tuning spatial and temporal control measures, which may be particularly important for early season infestations.展开更多
Spotted wing drosophila, <i>Drosophila suzukii</i> (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are parti...Spotted wing drosophila, <i>Drosophila suzukii</i> (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are particularly susceptible to infestation, and fruit producers are desperate for methods to control this pest. One of the keys to developing an integrated management program for SWD is to understand host preference and varietal susceptibility of highly susceptible crop hosts. Working in replicated small plots, experiments were conducted to evaluate differences in varietal susceptibility on cold hardy red primocane fruiting raspberries. Significant differences were observed in both the level of infestation and in the average number of larvae per berry by variety. In addition, it appears that there is a significant negative correlation between the level of infestation and the number of larvae per fruit with the time of sampling, but only an interaction of variety and time for the number of larvae per berry. These data provide a better understanding of the biology and ecology of this pest which is critical in refining current management practices. Knowledge of these interactions can aid in optimizing control strategies such as fine-tuning spatial and temporal control measures, which may be particularly important for early season infestations.展开更多
We examined mitotic chromosomes of three newly found members of the Drosophila obscura species group,D.luguensis,D.dianensis and D.limingi from Yunnan and compared their karyotypes to those of respective related speci...We examined mitotic chromosomes of three newly found members of the Drosophila obscura species group,D.luguensis,D.dianensis and D.limingi from Yunnan and compared their karyotypes to those of respective related species.D.luguensis possessed a diploid number of 12 chromosomes,comprising 3 pairs of metacentrics (V-shaped),2 pairs of acrocentrics (rod-like) and 1 pair of micro-chromosomes (dot-like).Both the X and Y were metacentrics.D.dianensis and D.limingi possessed a diploid number of 10 chromosomes,comprising 1 pair of large V-shaped,1 pair of moderate-sized V-shaped,2 pairs of submetacentric (J-shaped) chromosomes,and 1 pairs of dot-like chromosomes,with their X chromosomes were J-shaped and Y chromosomes were short rod-like ones.Based upon the results of chromosomal comparisons,geographic information of the sinobscura subgroup,as well inter-specific phylogenetic relationship deduced elsewhere,D.luguensis was considered to retain an ancestral form of the karyotype within this subgroup.The present observations have also implied that D.sinobscura (2n=12:2V,1J,2R,1D) might have derived from a sub-lineage of a pre-“sinobscura-hubeiensis” lineage by pericentric inversion of moderate-sized metacentric autosomes and D.hubeiensis (2n=10:4V,1D) from another sub-lineage of the same lineage by centric fusion of 2 pairs of acrocentric autosomes.Similar chromosomal changes of centric fusion,centric fission and/or pericentric inversion might have occurred during the course of species divergences between D.dianensis and D.subsilvestris (2n=12:3V,2R,1D),an European member closely related to D.dianensis,and between D.limingi and D.tsukubaensis (2n=12:3V,2R,1D),an East Asian member near to D.limingi.展开更多
Technology development has always been one of the forces driving breakthroughs in biomedical research. Since the time of Thomas Morgan, Drosophilists have, step by step, developed powerful genetic tools for manipulati...Technology development has always been one of the forces driving breakthroughs in biomedical research. Since the time of Thomas Morgan, Drosophilists have, step by step, developed powerful genetic tools for manipulating and functionally dissecting the Drosophila genome, but room for improving these technologies and developing new techniques is still large, especially today as biologists start to study systematically the functional genomics of different model organisms, including humans, in a high-throughput manner. Here, we report, for the first time in Drosophila, a rapid, easy, and highly specific method for modifying the Drosophila genome at a very high efficiency by means of an improved transcription activator-like effector nuclease （TALEN） strategy. We took advantage of the very recently developed ＂unit assembly＂ strategy to assemble two pairs of specific TALENs designed to modify the yellow gene （on the sex chromosome） and a novel autosomal gene. The mRNAs of TALENs were subsequently injected into Drosophila embryos. From 31.2% of the injected Fo fertile flies, we detected inheritable modification involving the yellow gene. The entire process from construction of specific TALENs to detection of inheritable modifications can be accomplished within one month. The potential applications of this TALEN-mediated genome modification method in Drosophila are discussed.展开更多
Recent advances in our ability to design DNA binding factors with specificity for desired sequences have resulted in a revolution in genetic engineering, enabling directed changes to the genome to be made relatively e...Recent advances in our ability to design DNA binding factors with specificity for desired sequences have resulted in a revolution in genetic engineering, enabling directed changes to the genome to be made relatively easily. Traditional techniques for generating genetic mutations in most organisms have relied on selection from large pools of randomly induced mutations for those of particular interest, or time-consuming gene targeting by homologous recombination. Drosophila melanogaster has always been at the forefront of genetic analysis, and application of these new genome editing techniques to this organism will revolutionise our approach to performing analysis of gene function in the future. We discuss the recent techniques that apply the CRISPR/Cas9 system to Drosophila, highlight potential uses for this technology and speculate upon the future of genome engineering in this model organism.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111123(to JQ)。
文摘Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
基金the National Natural Science Foundation of China(No.81970999)the Shanghai Rising Star Project(No.19QA1404900)。
文摘Drosophila melanogaster has been a popular model organism in the study of sleep and circadian rhythm.The Drosophila activity monitoring(DAM)system is one of the many tools developed for investigating sleep behavior in fruit flies and has been acknowledged by researchers around the world for its simplicity and cost-effectiveness.Based on the simple activity data collected by the DAM system,a wide range of parameters can be generated for sleep and circadian studies.However,current programs that analyze DAM data cover a limited number of metrics and fail to provide individual data for the user to plot graphs and conduct analysis using other software.Therefore,we have developed SleepyFlyR,an R package that:(1)is simple and easy to use with a user-friendly user interface script;(2)provides a comprehensive analysis of sleep and activity parameters;(3)generates double-plotted graphs for sleep and activity patterns;(4)offers visualization of sleep and activity profiles across multiple days or within a single day;(5)calculates the changes of sleep and activity parameters between baseline and experiment;(6)stores both summary data and individual data in files with unique title.
基金supported by the National Natural Science Foundation of China(32170484 and 32300384)the Fundamental Research Funds for the Central Universities(2572022DQ07 and 2572020AW04).
文摘Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.
基金supported by the National Natural Science Foundation of China(32371063,82341248,and 32071009)Guangdong Basic and Applied Basic Research Foundation(2024A1515011500)the Shenzhen Science and Technology Program(ZDSYS20200811142401005).
文摘Dear Editor,Sleep and memory are highly linked across species.Sleep gates and stabilizes memory,critical for memory processing.Insufficient sleep impairs cognition acutely/chronically,in vertebrates and invertebrates[1,2].While key elements are characterized[3,4],how a single molecule integrates sleep and memory remains unknown.
基金National Key Research and Development Program,Grant/Award Number:2022YFD1800505Hainan Province Science and Technology Special Fund,Grant/Award Number:ZDYF2024XDNY198+1 种基金Beijing Municipal Natural Science Foundation,Grant/Award Number:6232025Natural Science Foundation of China,Grant/Award Number:32272960。
文摘Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.
基金supported by National Key R&D Program of China(2023YFD2100205)Fuzhou Science&Technology Project,China(2022-Y-0022022-P-023).
文摘Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated that Lateolabrax japonicus peptides(LPH),rich in Glu,Gly,and hydrophobic amino acids,exhibited remarkable antioxidant activity in vitro,with though its action mechanism yet to be revealed.Therefore,to assess the in vivo antioxidative properties of LPH,we employed H_(2)O_(2) to generate oxidative stress in Drosophila melanogaster model.Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH’s enhancement of the antioxidant defense system and intestinal functions.Antioxidant effects were manifested by a decrease in malondialdehyde(MDA)levels,elevated superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)activities,decreased levels of reactive oxygen species(ROS)in intestinal epithelial cells,and the preservation of intestinal length.LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells.At the gene level,LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level.Furthermore,high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H_(2)O_(2)-induced Drosophila.These findings provide a deeper understanding of the antioxidative mechanism of LPH,suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.
基金funded by a grant from the Russian Science Foundation № 24-24-00354
文摘It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms.De novo genes frequently emerge in proximity to existing genes,forming gene overlaps.Here,we present an analysis of the evolutionary history of a putative de novo gene,lawc,which overlaps with the conserved Trf2 gene,which encodes a general transcription factor in Drosophila melanogaster.We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region(UTR)of Trf2 and displays an extensive spatiotemporal expression pattern.One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short,highly conserved regions located in Trf2 introns.This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved genes.The observed lawc expression pattern may be due to the overlap of lawc with the 5'-UTR of Trf2.This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.
基金supported by the National Natural Science Foundation of China(32371063,82341288,32071009)to C.L.Guangdong Basic and Applied Basic Research Foundation(2024A1515011500)to C.L.
文摘General anesthesia(GA)is a pharmacologically induced,reversible state characterized by unconsciousness,amnesia,analgesia,and immobility in response to noxious stimuli.Accumulating evidence from animal models has elucidated diverse mechanisms of the action underlying GA,including disruption of large-scale brain network connectivity,regulation of multiple neural pathways,and modulation of specific receptors and ion channels.Despite advances in dissecting the neurobiological basis of anesthetic action,the precise cellular and circuit-level processes remain incompletely understood,limiting the development of safer and more effective strategies.Recent studies in Drosophila melanogaster,a genetically tractable model organism offering robust genetic analysis,advanced imaging capabilities,and compact neural architecture,have yielded critical insights into the conserved neurobiological mechanisms of GA,offering translational value for mammalian systems.This review outlines:1)experimental paradigms used to evaluate anesthetic sensitivity and behavioral responses in Drosophila;2)molecular targets and their mechanistic roles in mediating GA;and 3)neural circuit architectures and activity patterns shared by GA and sleep.Cross-species comparisons are integrated to highlight conserved mechanisms that may guide the development of more refined anesthetic strategies.
文摘Neural stem cells(NSCs)play a fundamental role in generating diverse neuronal populations that contribute to the formation of intricate neural circuitry.Disturbances arising from intrinsic or extrinsic factors can alter the developmental behavior of NSCs and disrupt nervous system homeostasis.While intrinsic regulatory mechanisms have been elucidated extensively in invertebrate or vertebrate models,the regulatory mechanisms underlying extrinsic cues from the cellular environment remain poorly understood.This review synthesized recent research on cellular ambient effects,including the microenvironment,systemic environment and external factors,on NSCs in Drosophila.Key topics include spatial cues,NSC-glia interactions,long-distance regulation by tissues such as the fat body,and the external environmental stressors like irradiation or viral infection.By integrating these findings,this review provides new insights into how extrinsic signals shape NSCs and bridges gaps between foundational research and clinical translation.
基金financially supported by the National Natural Science Foundation of China(82402177,82171846,82422025,82471430)Clinical Medicine Plus X-Young Scholars Project of Peking University(PKU2025PKULCXQ026)+1 种基金National High Level Hospital Clinical Research Funding(Interdepartmental Research Project of Peking University First Hospital,2023IR51,High Quality Clinical Research Project of Peking University First Hospital,2022CR69)Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases(BZ0317).
文摘Spinocerebellar ataxia(SCA)type 51 is a neurodegenerative disease caused by CAG repeat expansions in exon 1 of the THAP11 gene.These repeats are translated into a glutamine-rich protein,THAP11-polyQ,which forms protein aggregates and exhibits toxicity in cell models;however,the underlying mechanism remains unclear.In this study,we generate transgenic Drosophila models expressing varying lengths of THAP11-polyQ using the UAS-GAL4 system and assess neurodegeneration through pathological and behavioral analyses.Our results demonstrate that expression of THAP11-polyQ in transgenic flies leads to progressive neuronal cell loss,locomotor deficiency,and reduced survival.RNA sequencing of patient-derived skin fibroblasts reveals significant enrichment of the PI3K–Akt–mTOR pathway,and electron microscopy of transgenic flies shows an increase in multilamellar bodies,suggesting involvement of autophagy in SCA51.Consequently,we treat the fly model with rapamycin,an mTOR inhibitor known to enhance autophagy.This treatment reduces toxic THAP11-polyQ protein aggregates,significantly alleviates neuronal degeneration,and improves locomotor function,consistent with the rescue effects observed upon overexpression of Atg8a.Overall,these findings suggest that the Drosophila model,which recapitulates the neurodegenerative features of SCA51,can be used to investigate pathogenic mechanisms and that rapamycin holds promising potential as a therapeutic approach for this disease.
基金Supported by Natural Science Foundation of Chongqing(2008BB1368)~~
文摘[ Objective ] The aim of this study was to investigate the infectivity of Nosema bombycis to drosophila, which offered a new vision for systematical studies on the infection mechanism of Nosema bombycis, and also provided reference for the bio-control effect of Nosema bombycis. [ Method ] Nosema bombycis was used to feed wild type and mutant drosophila, and the morphological observation of Nosema bombycis in drosophila body fluid was also analyzed by calcofluor white M2R fluorescent staining. [ Result] Nosema bombycis could infect drosophila, and the number of Nosema bombycis in the infected mutant drosophila was higher than that in wild type drosophila. [ Conclusion ] Nosema bombycis can infect drosophila, which provides primary reference for studies on the infectivity of Nosema bombycis to other hosts and also lays a foundation for further study on the infection mechanism of Nosema bombycis.
文摘Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.
文摘Spotted wing drosophila, Drosophila suzukii (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are particularly susceptible to infestation, and fruit producers are desperate for methods to control this pest. One of the keys to developing an integrated management program for SWD is to understand host preference and varietal susceptibility of highly susceptible crop hosts. Working in replicated small plots, experiments were conducted to evaluate differences in varietal susceptibility on cold hardy red primocane fruiting raspberries. Significant differences were observed in both the level of infestation and in the average number of larvae per berry by variety. In addition, it appears that there is a significant negative correlation between the level of infestation and the number of larvae per fruit with the time of sampling, but only an interaction of variety and time for the number of larvae per berry. These data provide a better understanding of the biology and ecology of this pest which is critical in refining current management practices. Knowledge of these interactions can aid in optimizing control strategies such as fine-tuning spatial and temporal control measures, which may be particularly important for early season infestations.
文摘Spotted wing drosophila, <i>Drosophila suzukii</i> (Matsumura) (SWD), is emerging as the most significant pest of berries and stone fruits worldwide. With a broad host range, thin-skinned berries are particularly susceptible to infestation, and fruit producers are desperate for methods to control this pest. One of the keys to developing an integrated management program for SWD is to understand host preference and varietal susceptibility of highly susceptible crop hosts. Working in replicated small plots, experiments were conducted to evaluate differences in varietal susceptibility on cold hardy red primocane fruiting raspberries. Significant differences were observed in both the level of infestation and in the average number of larvae per berry by variety. In addition, it appears that there is a significant negative correlation between the level of infestation and the number of larvae per fruit with the time of sampling, but only an interaction of variety and time for the number of larvae per berry. These data provide a better understanding of the biology and ecology of this pest which is critical in refining current management practices. Knowledge of these interactions can aid in optimizing control strategies such as fine-tuning spatial and temporal control measures, which may be particularly important for early season infestations.
文摘We examined mitotic chromosomes of three newly found members of the Drosophila obscura species group,D.luguensis,D.dianensis and D.limingi from Yunnan and compared their karyotypes to those of respective related species.D.luguensis possessed a diploid number of 12 chromosomes,comprising 3 pairs of metacentrics (V-shaped),2 pairs of acrocentrics (rod-like) and 1 pair of micro-chromosomes (dot-like).Both the X and Y were metacentrics.D.dianensis and D.limingi possessed a diploid number of 10 chromosomes,comprising 1 pair of large V-shaped,1 pair of moderate-sized V-shaped,2 pairs of submetacentric (J-shaped) chromosomes,and 1 pairs of dot-like chromosomes,with their X chromosomes were J-shaped and Y chromosomes were short rod-like ones.Based upon the results of chromosomal comparisons,geographic information of the sinobscura subgroup,as well inter-specific phylogenetic relationship deduced elsewhere,D.luguensis was considered to retain an ancestral form of the karyotype within this subgroup.The present observations have also implied that D.sinobscura (2n=12:2V,1J,2R,1D) might have derived from a sub-lineage of a pre-“sinobscura-hubeiensis” lineage by pericentric inversion of moderate-sized metacentric autosomes and D.hubeiensis (2n=10:4V,1D) from another sub-lineage of the same lineage by centric fusion of 2 pairs of acrocentric autosomes.Similar chromosomal changes of centric fusion,centric fission and/or pericentric inversion might have occurred during the course of species divergences between D.dianensis and D.subsilvestris (2n=12:3V,2R,1D),an European member closely related to D.dianensis,and between D.limingi and D.tsukubaensis (2n=12:3V,2R,1D),an East Asian member near to D.limingi.
基金supported by the grants from the 973 Program(Nos.2009CB918702 and 2012CB945101)the NSFC(Nos.31071087 and 31100889)+1 种基金W.-M.D.is supported by NIH grant R01GM072562National Science Foundation of USA(IOS-1052333)
文摘Technology development has always been one of the forces driving breakthroughs in biomedical research. Since the time of Thomas Morgan, Drosophilists have, step by step, developed powerful genetic tools for manipulating and functionally dissecting the Drosophila genome, but room for improving these technologies and developing new techniques is still large, especially today as biologists start to study systematically the functional genomics of different model organisms, including humans, in a high-throughput manner. Here, we report, for the first time in Drosophila, a rapid, easy, and highly specific method for modifying the Drosophila genome at a very high efficiency by means of an improved transcription activator-like effector nuclease （TALEN） strategy. We took advantage of the very recently developed ＂unit assembly＂ strategy to assemble two pairs of specific TALENs designed to modify the yellow gene （on the sex chromosome） and a novel autosomal gene. The mRNAs of TALENs were subsequently injected into Drosophila embryos. From 31.2% of the injected Fo fertile flies, we detected inheritable modification involving the yellow gene. The entire process from construction of specific TALENs to detection of inheritable modifications can be accomplished within one month. The potential applications of this TALEN-mediated genome modification method in Drosophila are discussed.
基金supported by the UK Medical Research Council and the European Research Council (DARCGENs, No. 249869)
文摘Recent advances in our ability to design DNA binding factors with specificity for desired sequences have resulted in a revolution in genetic engineering, enabling directed changes to the genome to be made relatively easily. Traditional techniques for generating genetic mutations in most organisms have relied on selection from large pools of randomly induced mutations for those of particular interest, or time-consuming gene targeting by homologous recombination. Drosophila melanogaster has always been at the forefront of genetic analysis, and application of these new genome editing techniques to this organism will revolutionise our approach to performing analysis of gene function in the future. We discuss the recent techniques that apply the CRISPR/Cas9 system to Drosophila, highlight potential uses for this technology and speculate upon the future of genome engineering in this model organism.
