Genetics最新文献_第6页

A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation. E2F转录因子和内质网应激传感器IRE1在细胞质DNA积累中的新作用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-11 DOI: 10.1093/genetics/iyaf190

Arghya Das, Yining Li, Yiting Fan, Nam-Sung Moon

{"title":"A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation.","authors":"Arghya Das, Yining Li, Yiting Fan, Nam-Sung Moon","doi":"10.1093/genetics/iyaf190","DOIUrl":"https://doi.org/10.1093/genetics/iyaf190","url":null,"abstract":"The E2F family of transcription factors are key regulators of the cell cycle in all metazoans. While they are primarily known for their role in cell cycle progression, E2Fs also play broader roles in cellular physiology, including the maintenance of exocrine tissue homeostasis. However, the underlying mechanisms that render exocrine cells particularly sensitive to E2F deregulation remain poorly understood. The Drosophila larval salivary gland (SG), like its mammalian counterpart, is an exocrine tissue that produces large quantities of \"glue proteins\" in the endoplasmic reticulum (ER). Here, we show that E2F activity is important for the exocrine function of the Drosophila SG. The loss of de2f1b, an alternatively spliced isoform of Drosophila E2F1, leads to elevated DNA damage and accumulation of cytoplasmic DNA (cytoDNA) in the SGs. Surprisingly, we found that IRE1, a key sensor of the unfolded protein response, is required for ER homeostasis during development that is critical for preventing cytoDNA accumulation in the SG. Importantly, we found evidence demonstrating that IRE1 activity is attenuated in de2f1b-deficient SGs, contributing to ER dysfunction and cytoDNA accumulation. Together, these findings reveal an unanticipated link between ER homeostasis and cytoDNA processing and offer mechanistic insights into why exocrine tissues are particularly vulnerable to E2F deregulation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Signatures of selective sweeps in continuous-space populations. 连续空间种群中选择性扫描的特征。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-10 DOI: 10.1093/genetics/iyaf183

Meera Chotai, Xinzhu Wei, Philipp W Messer

{"title":"Signatures of selective sweeps in continuous-space populations.","authors":"Meera Chotai, Xinzhu Wei, Philipp W Messer","doi":"10.1093/genetics/iyaf183","DOIUrl":"10.1093/genetics/iyaf183","url":null,"abstract":"Selective sweeps describe the process by which an adaptive mutation arises and rapidly fixes in the population, thereby removing genetic variation in its genomic vicinity. The expected signatures of selective sweeps are relatively well understood in panmictic population models, yet natural populations often extend across larger geographic ranges where individuals are more likely to mate with those born nearby. To investigate how such spatial population structure can affect sweep dynamics and signatures, we simulated selective sweeps in populations inhabiting a two-dimensional continuous landscape. The maximum dispersal distance of offspring from their parents can be varied in our simulations from an essentially panmictic population to scenarios with increasingly limited dispersal. We find that in low-dispersal populations, adaptive mutations spread more slowly than in panmictic ones, while recombination becomes less effective at breaking up genetic linkage around the sweep locus. Together, these factors result in a trough of reduced genetic diversity around the sweep locus that looks very similar across dispersal rates. We also find that the site frequency spectrum around hard sweeps in low-dispersal populations is enriched for intermediate-frequency variants, making these sweeps appear softer than they are. Furthermore, haplotype heterozygosity at the sweep locus tends to be elevated in low-dispersal scenarios as compared to panmixia, contrary to what is observed in neutral scenarios without sweeps. The haplotype patterns generated by these hard sweeps in low-dispersal populations can resemble soft sweeps from standing genetic variation that arose from substantially older alleles. Our results highlight the need for better accounting for spatial population structure when making inferences about selective sweeps.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cycloheximide resistant ribosomes reveal adaptive translation dynamics in C. elegans. 环己亚胺抗性核糖体揭示秀丽隐杆线虫的适应性翻译动力学。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-10 DOI: 10.1093/genetics/iyaf189

Qiuxia Zhao, Blythe Bolton, Reed Rothe, Reiko Tachibana, Can Cenik, Elif Sarinay Cenik

{"title":"Cycloheximide resistant ribosomes reveal adaptive translation dynamics in C. elegans.","authors":"Qiuxia Zhao, Blythe Bolton, Reed Rothe, Reiko Tachibana, Can Cenik, Elif Sarinay Cenik","doi":"10.1093/genetics/iyaf189","DOIUrl":"10.1093/genetics/iyaf189","url":null,"abstract":"Protein translation regulation is critical for cellular responses and development, yet how elongation stage disruptions shape these processes remains incompletely understood. Here, we identify a single amino acid substitution (P55Q) in the ribosomal protein RPL-36A of Caenorhabditis elegans that confers complete resistance to the elongation inhibitor cycloheximide (CHX). Heterozygous animals carrying both wild-type RPL-36A and RPL-36A(P55Q) develop normally but show intermediate CHX resistance, indicating a partial dominant effect. Leveraging RPL-36A(P55Q) as a single-copy positive selection marker for CRISPR-based genome editing, we introduced targeted modifications into multiple ribosomal protein genes, confirming its broad utility for altering essential loci. In L4-stage heterozygotes, where CHX-sensitive and CHX-resistant ribosomes coexist, ribosome profiling revealed increased start-codon occupancy, reduced disome formation, and no codon-specific pausing. Surprisingly, chronic CHX treatment did not activate canonical stress pathways (RQC, RSR, ISR), as indicated by the absence of RPS-10 ubiquitination, eIF2α or PMK-1 phosphorylation, or ATF-4 induction. Instead, RNA-normalized ribosome footprints revealed selective changes in translation efficiency, with reduced nucleolar/P-granule components and increased oocyte development genes. Consistently, premature oocyte development was observed in L4 animals. These findings suggest that partial inhibition of translation elongation disrupts developmental timing across tissues, likely by altering translation efficiency.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A model-free method for genealogical inference without phasing and its application for topology weighting. 无模型无相位谱系推理方法及其在拓扑加权中的应用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-08 DOI: 10.1093/genetics/iyaf181

Simon H Martin

{"title":"A model-free method for genealogical inference without phasing and its application for topology weighting.","authors":"Simon H Martin","doi":"10.1093/genetics/iyaf181","DOIUrl":"https://doi.org/10.1093/genetics/iyaf181","url":null,"abstract":"Recent advances in methods to infer and analyse ancestral recombination graphs (ARGs) are providing powerful new insights in evolutionary biology and beyond. Existing inference approaches tend to be designed for use with fully-phased datasets, and some rely on model assumptions about demography and recombination rate. Here I describe a simple model-free approach for genealogical inference along the genome from unphased genotype data called Sequential Tree Inference by Collecting Compatible Sites (sticcs). sticcs applies a heuristic algorithm based on the perfect phylogeny principle to reconstruct a local genealogy at each variant site in the genome, using a 'collecting' procedure to import information from other nearby sites. Using simulations, I show that sticcs is accurate for ARG inference, but only when the sample size is small. However, I also describe how it can be applied for the purpose of topology weighting by 'stacking' tree sequences inferred for multiple subsets of the data, removing the sample size restriction. Topology weights estimated in this way from unphased data tend to be more accurate than those computed with full ARGs inferred from perfectly phased data using several popular tools. The methods presented therefore have promise for analysis of relatedness and introgression in non-model species, including polyploids. The new methods are implemented in two Python packages, sticcs (for ARG inference) and twisst2 (for topology weighting using the stacking procedure), both of which interface with the tskit library for analysis of tree sequence objects.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans. 线粒体sirtuins sir-2.2和sir-2.3调节线虫的寿命。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-05 DOI: 10.1093/genetics/iyaf185

Sarah M Chang, Latisha P Franklin, Sampurna Sattar, Corinna A Moro, Michael V DeGennaro, Nicole G LaGanke, Wendy Hanna-Rose

{"title":"Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans.","authors":"Sarah M Chang, Latisha P Franklin, Sampurna Sattar, Corinna A Moro, Michael V DeGennaro, Nicole G LaGanke, Wendy Hanna-Rose","doi":"10.1093/genetics/iyaf185","DOIUrl":"10.1093/genetics/iyaf185","url":null,"abstract":"Mitochondrial sirtuins regulate metabolism and are emerging drug targets for metabolic and age-related diseases such as cancer, diabetes, and neurodegeneration. Yet, the extent of their functions remain unclear. Here, we uncover a physiological role for the C. elegans mitochondrial sirtuins, sir-2.2 and sir-2.3, in lifespan regulation. Using genetic alleles with deletions that destroy catalytic activity, we demonstrate that sir-2.2 and sir-2.3 mutants live an average of 25% longer than controls when fed the normal lab diet of live E. coli OP50. While decreased consumption of food is a known mechanism for lifespan extension, we did not find evidence of reduced pharyngeal pumping. Interestingly, lifespan extension effected by loss of sir-2.2 or sir-2.3 is sensitive to the diet. The lifespan extension of the sir-2.2 mutants is eliminated and that of sir-2.3 mutants is attenuated when the animals are fed the E. coli strain HT115, which is typically used for RNAi experiments. We used growth ability of the food source and a virulent pathogenic strain to ask if differences in pathogenicity are related to the mechanisms for lifespan extension. sir-2.3 deletion results in lifespan extension in all conditions. However, removing the ability of the food source to grow eliminated the sir-2-mediated effect. We also examine the response of the mutants to oxidative stress, and our results suggest that a hormetic response contributes to lifespan extension in both mutants. Our data suggest that sir-2.2 and sir-2.3 use overlapping yet distinct mechanisms for regulating lifespan.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phantom epistasis through the lens of genealogies. 从家谱的角度看幻影上位。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-05 DOI: 10.1093/genetics/iyaf184

Anastasia Ignatieva, Lino A F Ferreira

{"title":"Phantom epistasis through the lens of genealogies.","authors":"Anastasia Ignatieva, Lino A F Ferreira","doi":"10.1093/genetics/iyaf184","DOIUrl":"https://doi.org/10.1093/genetics/iyaf184","url":null,"abstract":"Phantom epistasis arises when, in the course of testing for gene-by-gene interactions, the omission of a causal variant with a purely additive effect on the phenotype causes the spurious inference of a significant interaction between two SNPs. This is more likely to arise when the two SNPs are in relatively close proximity, so while true epistasis between nearby variants could be commonplace, in practice there is no reliable way of telling apart true epistatic signals from false positives. By considering the causes of phantom epistasis from a genealogy-based perspective, we leverage the rich information contained within reconstructed genealogies (in the form of ancestral recombination graphs) to address this problem. We propose a novel method for explicitly quantifying the genealogical evidence that a given pairwise interaction is the result of phantom epistasis, which can be applied to pairs of SNPs regardless of the genetic distance between them. Our method uses only publicly available data and so does not require access to the phenotypes and genotypes used for detecting interactions. Using simulations, we show that the method has excellent performance at even low genetic distances (around 0.5cM), and demonstrate its power to detect phantom epistasis using real data from previous studies. This opens up the exciting possibility of distinguishing spurious interactions in cis from those reflecting real biological effects.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revealing function-altering MECP2 mutations in individuals with autism spectrum disorder using yeast and Drosophila. 利用酵母和果蝇揭示自闭症谱系障碍个体功能改变的MECP2突变。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf121

Eric Chen, Jessica Schmitt, Graeme McIntosh, Barry P Young, Tianshun Lian, Jie Liu, Kexin K Chen, J Beatrice Liston, Lily MacDonald, Bill Wang, Sonia Medina Giro, Benjamin Boehme, Mriga Das, Seevasant Indran, Jesse T Chao, Sanja Rogic, Paul Pavlidis, Douglas W Allan, Christopher J R Loewen

{"title":"Revealing function-altering MECP2 mutations in individuals with autism spectrum disorder using yeast and Drosophila.","authors":"Eric Chen, Jessica Schmitt, Graeme McIntosh, Barry P Young, Tianshun Lian, Jie Liu, Kexin K Chen, J Beatrice Liston, Lily MacDonald, Bill Wang, Sonia Medina Giro, Benjamin Boehme, Mriga Das, Seevasant Indran, Jesse T Chao, Sanja Rogic, Paul Pavlidis, Douglas W Allan, Christopher J R Loewen","doi":"10.1093/genetics/iyaf121","DOIUrl":"10.1093/genetics/iyaf121","url":null,"abstract":"Pathogenic variants in MECP2 commonly lead to Rett syndrome, where MECP2's function as a DNA cytosine methylation reader is believed critical. MECP2 variants are also cataloged in individuals with autism spectrum disorder (ASD), including nine missense variants which had no known clinical significance at the start of this study. To assess these nine variants as risk alleles for ASD, we developed MECP2 variant functional assays using budding yeast and Drosophila. We calibrated these assays with known pathogenic and benign variants. Our data predict that four ASD variants are loss of function and five are functional. Protein destabilization offers insight into the altered function of some of these variants. Notably, yeast and Drosophila lack DNA methylation, yet all Rett pathogenic and ASD variants located in the methyl DNA-binding domain that we analyzed proved to be loss of function, suggesting a clinically relevant role for non-methyl DNA-binding by MECP2.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A species-specific nuclear receptor was integrated into a developmental polyphenism pathway. 一个物种特异性的核受体被整合到发育多表型途径中。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf140

Eleni Katsougia, Samantha J Connors, Erik J Ragsdale

{"title":"A species-specific nuclear receptor was integrated into a developmental polyphenism pathway.","authors":"Eleni Katsougia, Samantha J Connors, Erik J Ragsdale","doi":"10.1093/genetics/iyaf140","DOIUrl":"10.1093/genetics/iyaf140","url":null,"abstract":"Polyphenism, the ability of an organism to develop discrete, alternative forms of a trait in response to environmental signals, relies on molecular switches to guide developmental trajectories. In the nematode Pristionchus pacificus, such a switch produces a dimorphism in its adult feeding structures, enabling individuals to develop as either microbivores or predators based on the environments they experience before adulthood. Several regulators of this polyphenism are known, giving an opportunity to determine the ultimate molecular targets of a plastic transcriptional response and to reconstruct their evolutionary fates. Because nuclear receptors (NRs) are rapid molecular sensors of intrinsic and sometimes extrinsic signals, they provide likely candidates to link a switch mechanism to the alternative phenotypes produced. Here, we report the results of a reverse genetic screen of NRs, specifically those whose expression is influenced by the polyphenism, for their possible influence on polyphenism-related traits. Our screen identified a gene, pnhr-3, that influences the sensitivity of the polyphenism in P. pacificus. Phylogenetic analysis and microsynteny show that pnhr-3 is unique to this species. Additionally, its parent gene does not show polyphenism-biased expression, indicating that this new gene was recently recruited into an established molecular pathway. Along with 3 other NRs, which are also lineage-specific relative to outgroups that lack the polyphenism, pnhr-3 impacts other traits that also respond to resource conditions, influencing a polyphenism. Our findings highlight the short time scale in which a recently duplicated transcription factor with new putative regulatory sequences can be adopted into a regulatory pathway for plastic development.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptive gene expression parallelism in the male reproductive tract of two Drosophila species. 两种果蝇雄性生殖道适应性基因表达的平行性。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf113

Tiezheng Fan, Julie M Cridland, David J Begun

{"title":"Adaptive gene expression parallelism in the male reproductive tract of two Drosophila species.","authors":"Tiezheng Fan, Julie M Cridland, David J Begun","doi":"10.1093/genetics/iyaf113","DOIUrl":"10.1093/genetics/iyaf113","url":null,"abstract":"While stabilizing selection is likely an important process leading to conserved phylogenetic patterns of gene expression, the role of selection in driving expression divergence among populations and species is much less clear. One approach for identifying adaptation is to document parallel evolution, the independent evolution of similar phenotypes in multiple species in response to similar selective pressures. Latitudinal clines are a classic system for studying adaptation in many species, including Drosophila; multiple species exhibit clines for several phenotypes, such as body and wing size. However, the extent of latitudinal transcriptome variation and the degree to which such variation is shaped by selection remain unclear. Here, we investigate transcriptomes of North American Drosophila melanogaster and Drosophila simulans with a focus on the male reproductive tract. For both species, we sampled accessory glands and testis from lines derived from 2 locations, 1 low latitude (Panama City, Panama), and 1 high latitude (Maine, USA). We observed a striking similarity between species in the directionality and magnitude of latitudinal expression variation in the accessory gland but not in the testis. This suggests that selection has fine-tuned accessory gland transcript abundance in a similar manner in response to latitudinal selection pressures in both species. In addition to gene level parallelism, these species exhibit correlated fluctuations of low vs high latitude expression differences on a larger chromosomal scale. Analysis of whole male transcriptomes from the same population samples suggests that parallel latitudinal selection responses play an important role in expression adaptation for both species.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melanization regulates wound healing by limiting polyploid cell growth in the Drosophila epithelium. 黑化通过限制果蝇上皮中多倍体细胞的生长来调节伤口愈合。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf109

Loiselle Gonzalez-Baez, Elizabeth Mortati, Lillie Mitchell, Vicki P Losick

{"title":"Melanization regulates wound healing by limiting polyploid cell growth in the Drosophila epithelium.","authors":"Loiselle Gonzalez-Baez, Elizabeth Mortati, Lillie Mitchell, Vicki P Losick","doi":"10.1093/genetics/iyaf109","DOIUrl":"10.1093/genetics/iyaf109","url":null,"abstract":"Wound healing requires a localized response that restricts growth, remodeling, and inflammation to the site of injury. In the fruit fly, Drosophila melanogaster, the epithelium heals puncture wounds through cell growth instead of cell division. Epithelial cells on wound margin both fuse and duplicate their genome to generate a multinucleated, polyploid cell essential for tissue repair. Despite the essential role of polyploidy in wound healing, the signals that initiate and regulate the extent of cell growth at the wound site remain poorly understood. One of the first steps in wound healing requires the deposit of melanin at the site of injury, which persists as a melanin scar. The melanin scar forms within hours after a puncture wound and is dependent on the activation of 3 prophenoloxidase genes (PPO1, PPO2, and PPO3). Using a triple loss of function mutant (PPOnull), we have uncovered a novel role for melanization in regulating wound healing by limiting polyploid cell growth post injury. Thus, melanization is required for efficient wound closure and its loss leads to an unexpected exacerbation of polyploid cell growth in the surrounding epithelial cells. This occurs, in part, through the early entry of epithelial cells into the endocycle, which may be due to altered gene expression as a result of delayed JNK signaling and other pathways. In conclusion, we have found that polyploid cell growth requires melanization at the injury site to control the extent of cell growth and regulate wound repair.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0