drosophila as a model organism pdf

Mutations in the IMD pathway and mustard counter Vibrio cholerae suppression of intestinal stem cell division in Drosophila. Genetics 186, 735755. We acknowledge Qatar University (QUST-1-CHS-2020-4) for funding this publication. Cell Microbiol. Roman G, Endo K, Zong L, Davis RL. (2011). The role of larval fat cells in adult Drosophila melanogaster. 2014;68:1528. ISSN 1740-634X (online) V. cholerae toxin, in turn, was shown to decrease intestinal stem cell division, alter epithelial regeneration, and induce cellcell junctional damage (Guichard et al., 2013; Wang et al., 2013). doi: 10.1128/IAI.01637-07, Kocks, C., Cho, J. H., Nehme, N., Ulvila, J., Pearson, A. M., Meister, M., et al. 28, 449462.e5. Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY. The cricket paralysis virus (CrPV), an RNA virus that infects a wide range of insect hosts, displays increased virulence with higher viral loads in IMD mutant flies (Costa et al., 2009). Genome Res 11: 11141125. (2018). Genetics. Chromosome studies in the Diptera. doi: 10.1016/j.molimm.2019.03.008, Costa, A., Jan, E., Sarnow, P., and Schneider, D. (2009). The authors then fed erlotinib to ethanol-consuming rats, and found that it reduced ethanol, but not sucrose or water intake (Corl et al, 2009). Addict Biol 19: 392401. The Anthrax toxin produced by Bacillus anthracis is comprised of protective antigen (PA), edema factor (EF), and lethal factor (LF) (Lacy and Collier, 2002). 18, 552560. Cook RK, Christensen SJ, Deal JA, Coburn RA, Deal ME, Gresens JM, Kaufman TC, Cook KR. Undertaker, a Drosophila Junctophilin, links Draper-mediated phagocytosis and calcium homeostasis. (2010). 2017;206:66589. Chan CC, Scoggin S, Wang D, Cherry S, Dembo T, Greenberg B et al (2011). doi: 10.1038/nature03957, Yagi, R., Mayer, F., and Basler, K. (2010). 10, 2328. Insect Biochem. Krz or Ulp1 Drosophila larval mutants exhibit inflammation-like phenotypes characterized by elevation in lamellocyte production, formation of melanotic tumors, accumulation of transcriptional effectors (Dorsal and Dif) of the Toll pathway, and increased expression of anti-microbial peptides (Drosomycin). doi: 10.1111/j.1462-5822.2006.00688.x, Zhao, P., Li, J., Wang, Y., and Jiang, H. (2007). Chemical mutagens, transposons, and transgenes to interrogate gene function in Drosophila melanogaster. Science. Chen ZX, Sturgill D, Qu J, Jiang H, Park S, et al. 7:13823. doi: 10.1038/ncomms13823, Medvedev, A. E., Murphy, M., Zhou, H., and Li, X. Rapid virulence annotation (RVA): identification of virulence factors using a bacterial genome library and multiple invertebrate hosts. Virol. In this review, we provide an overview of the use of Drosophila in hostpathogen interaction studies and highlight the role of the fly's innate immune system in pathogen control. Proc. Because fly acquisition of preference likely involves reward-related processes, the 70 SNPs in human RSU1 were tested for association with altered brain activity during reward anticipation using functional imaging. One of the best-studied autism genes is FMR1 that is also responsible for causing fragile X syndrome (FXS). Candida albicans Cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models. The pathogenic properties of a novel and conserved gene product, KerV, in proteobacteria. Front. Pharmac Rev. : Use of Drosophila as a Model Organism in Neuropsychopharmacology Research. Nat. Unlike mammals that have only one Dicer gene, and which is difficult to study, flies possess two genes, Dicer1 and Dicer2, that are required for processing miRNA precursors from pre-miRNA and siRNA precursors from long dsRNA, respectively (Robles-Sikisaka et al., 2001). doi: 10.1111/sji.12170, Nappi, A. J., Carton, Y., and Frey, F. (1991). 9, 106119. Several studies in Drosophila reported that loss-of-function mutations in essential RNAi pathway genes increase host vulnerability to viral infection (Zambon et al., 2006; Aliyari et al., 2008; Buchon et al., 2014). Microbiol. Proc. (2018). 9 Altmetric Metrics Abstract Drosophila melanogaster provides an important resource for in vivo modifier screens of neurodegenerative diseases. 5:e1000582. Cyanide produced by human isolates of Pseudomonas aeruginosa contributes to lethality in Drosophila melanogaster. Hairy transcriptional repression targets and cofactor recruitment in Drosophila. A single strand of this siRNA gets incorporated into the RISC complex and act as a template to recognize complementary mRNA, resulting in mRNA cleavage and therefore silencing of viral RNA. Infect. Plasmatocytes account for more than 90% of all mature larval hemocytes and are involved in the phagocytic elimination of pathogenic microorganisms and dead cells (Lemaitre and Hoffmann, 2007). Commonly, people consider three domains of validity. If they are sexually frustrated and are prevented from mating, they drink more alcohol (Shohat-Ophir et al, 2012). dNRAMP mutant flies were shown to be protected from viral infection (Rose et al., 2011). He B, Caudy A, Parsons L, Rosebrock A, Pane A, et al. Pharmacol Ther. Immunity 30, 588598. There are two broad categories: substance abuse and substance dependence. Inbreeding, cross-breeding and sterility in Drosophila. doi: 10.1146/annurev.en.40.010195.000335, Stroschein-Stevenson, S. L., Foley, E., O'Farrell, P. H., and Johnson, A. D. (2006). Among those genes is the macroglobulin-related protein (Mcr), which specifically opsonize Candida, unlike TEP2 and TEP3 that are needed for opsonization and efficient uptake of E. coli and S. aureus, respectively (Stroschein-Stevenson et al., 2006). Moreover, global gene expression analysis of Drosophila gut tissues to oral Erwinia carotovora infection revealed an important contribution of IMD and JAK/STAT pathways, but not the Toll pathway, to the regulation of gut immune responses (Buchon et al., 2009c). doi: 10.1016/S0092-8674(01)00547-5, Oh, C. T., Moon, C., Jeong, M. S., Kwon, S. H., and Jang, J. doi: 10.1126/science.1116008, PubMed Abstract | CrossRef Full Text | Google Scholar, Agaisse, H., and Perrimon, N. (2004). A novel system for the launch of alphavirus RNA synthesis reveals a role for the Imd pathway in arthropod antiviral response. In Manduca sexta, however, 6094% killing of a broad spectrum of gram-negative bacterial species including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium, and 5299% killing of gram-positive bacterial species including Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, and Micrococcus luteus was reported in an active melanotic milieu (Zhao et al., 2007). Research on the karyotype and evolution of Drosophila melanogaster species group. doi: 10.1126/science.1070948, Liao, J.-F., Wu, C.-P., Tang, C.-K., Tsai, C.-W., Rouhov, L., and Wu, Y.-L. (2019). Glinka S, Ometto L, Mousset S, Stephan W, De Lorenzo D. Demography and natural selection have shaped genetic variation in Drosophila melanogaster: a multi-locus approach. Flies cope with uncontrollable stress by learned helplessness. 224, 3133. Sci. This caveat, however, applies to all animal models of some human disorders. In mammals, other antiviral defense strategies, including protein sensors that recognize viral dsRNA motifs, have been identified. The peptidoglycan recognition protein PGRP-LE regulates the Drosophila immune response against the pathogen Photorhabdus. This crucial role of Ars2 in these small RNA pathways delivers novel insight into the biogenesis of small RNAs, a platform that could be extended to other systems (Sabin et al., 2009). (1) Face validity that asks whether the models look like the disease, that is, whether it recapitulates salient features or characteristic symptoms of the human affliction. Unexpected role of the IMD pathway in Drosophila gut defense against Staphylococcus aureus. Nature 343: 536540. doi: 10.1073/pnas.0708110105, Kounatidis, I., and Ligoxygakis, P. (2012). The rapid generation time (1 week) and . Because SZ is highly heritable (Tandon et al, 2008), one might be tempted to use a genetically tractable organism such as flies to model phenotypes associated with it. (2005). Therefore, the expression of the GOI (cDNA, including tags such as HA or fluorescent markers such as GFP; human gene; RNAi for transcript knockdown) can be driven in any of these patterns by crossing the appropriate Gal4 driver line to flies that carry the UASGOI transgene to express the protein of interest (POI). Schuckit MA, Smith TL, Kalmijn J (2004). Biophys. JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection. The concept that heritable traits are carried on chromosomes was first developed in the fly, as well as many other landmark discoveries in genetics (Sturtevant, 1967). Innate immune recognition of viral infection. Immunol. Furthermore, commonly used techniques and tools with Drosophila models will be briefly described, with a special emphasis on the advantages of Drosophila models in the study of various human diseases. Immunol. commonly used model organisms are Zebrafish, Why is experimenting with model organisms feasible? J. Interestingly, the Vibrio polysaccharide (VPS)-dependent biofilm, which is highly activated upon entry into the arthropod intestine, is essential for Drosophila intestinal colonization (Purdy and Watnick, 2011). Article doi: 10.1111/j.1462-5822.2005.00607.x, Benguettat, O., Jneid, R., Soltys, J., Loudhaief, R., Brun-Barale, A., Osman, D., et al. A role for GABA mechanisms in the motivational effects of alcohol. Certain disorders are never going to have any face validity in flies, such as suicidal impulses. Front. Tauber JM, Vanlandingham PA, Zhang B (2011). Cambridge: Cambridge University Press. (2000). Zhang YQ, Broadie K (2005). 1959;33:283325. Drosophila melanogaster is a small, common fly found near unripe and rotted fruit. 7, 799810. Comp. Proc. This began to be realized in the 1980s, when many developmental genes were discovered in the fly that specify the body plan of this insect. Key facts. 84, 11501157. Google Scholar. doi: 10.1128/JCM.36.11.3239-3242.1998, Guichard, A., Cruz-Moreno, B., Aguilar, B., van Sorge, N. M., Kuang, J., Kurkciyan, A. Broad-spectrum antimicrobial activity of the reactive compounds generated in vitro by Manduca sexta phenoloxidase. Unlike the mammalian Toll pathway, the activation of Drosophila Toll signaling is not initiated by direct interaction with microbial determinants, but rather by the cleaved form of sptzle, a cytokine-like molecule that is thought to be processed by secreted serine proteases (SPs) and sptzle-processing enzyme (SPE). Nature 287, 795801. S. aureus-infected dltA mutant flies exhibited an increase in life span compared to flies expressing dltA normally (Tabuchi et al., 2010). (2006). Nature 458, 346350. PLoS Pathog. doi: 10.1038/sj.emboj.7600466, Tang, H., Kambris, Z., Lemaitre, B., and Hashimoto, C. (2008). Pooled CRISPR Screens in Drosophila cells. Natl. A short history and description of Drosophila melanogaster classical genetics: chromosome aberrations, forward genetic screens, and the nature of mutations. doi: 10.1371/journal.pone.0007167, Anjum, S. G., Xu, W., Nikkholgh, N., Basu, S., Nie, Y., Thomas, M., et al. Complimentary expression profile studies identified 45 genes, including the SR-C1 scavenger receptor gene that is down-regulated upon Serpent depletion (Meister and Tuschl, 2004; Haasnoot and Berkhout, 2006). (1995). doi: 10.1016/j.jinsphys.2012.08.003, Cerenius, L., Lee, B. L., and Sderhll, K. (2008). However, fly researchers are developing an increasingly precise anatomical toolkit that allows for Gal4-mediated gene manipulation in ever more spatially restricted neurons. Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila. (A) Represents a schematic diagram of the Toll pathway. 23, 23332344. Immunol. Upon entry into the cells, viruses shed their shielding external coat, uncovering their RNA, and forming dsRNA. 129:e111. Internet Explorer). and JavaScript. doi: 10.1111/j.1744-7917.2008.00185.x, Griffen, A. L., Becker, M. R., Lyons, S. R., Moeschberger, M. L., and Leys, E. J. PLoS Pathog. Furthermore, no biological biomarkers are available to objectively diagnose the disease. Cas5 transcription in Candida albicans regulates cell wall integrity and is essential for fungal virulence in both murine and Toll mutant flies (Chamilos et al., 2009). Drosophila Models for Human Diseases pp 110Cite as, 1 The existence of a wide array of molecular and genetic tools that allow gene manipulation in specific cells/tissues in the fly also favors its use in hostpathogen interaction studies. PubMed doi: 10.1101/gad.1827009, Buchon, N., Broderick, N. A., Poidevin, M., Pradervand, S., and Lemaitre, B. High-resolution analysis of ethanol-induced locomotor stimulation in Drosophila. One might be hard pressed to model the positive symptoms of schizophrenia (SZ), such as hallucinations, in animals. Science 284, 19911994. doi: 10.1016/j.cell.2006.10.046, Govind, S. (2008). The genetics of behavioral alcohol responses in Drosophila. (2004). Genes 11:234. doi: 10.3390/genes11020234, Cherry, S. (2008). Cell 124, 783801. Proc. Ghezzi A, Krishnan HR, Atkinson NS (2012). Spn1 regulates the GNBP3-dependent Toll signaling pathway in Drosophila melanogaster. Annu. (2002a). The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila. doi: 10.1074/jbc.M111.333807, Sjoberg, B. M., and Torrents, E. (2011). Proc Natl Acad Sci USA 101: 65366541. Mutations affecting segment number and polarity in Drosophila. 287, 2166321672. Masamitsu Yamaguchi . Mechanisms of gene silencing by double-stranded RNA. 1967;55:37586. Hall JC (1977). doi: 10.1038/ni1303, Kemp, C., Mueller, S., Goto, A., Barbier, V., Paro, S., Bonnay, F., et al. Drosophila as a Model Organism to Study Basic Mechanisms of Longevity by Anna A. Ogienko 1, Evgeniya S. Omelina 1,2, Oleg V. Bylino 3, Mikhail A. Batin 4, Pavel G. Georgiev 3 and Alexey V. Pindyurin 1,* 1 Department of Regulation of Genetic Processes, Institute of Molecular and Cellular Biology SB RAS, 630090 Novosibirsk, Russia 2 Erwinia carotovora Evf antagonizes the elimination of bacteria in the gut of Drosophila larvae. Hammond MP, Laird CD. Drosophila D1 dopamine receptor mediates caffeine-induced arousal. Upregulation of Spn1, a member of the serpin superfamily protease inhibitors located upstream of SPE, for example, contributes to the Toll pathway inactivation and to a downregulation in the expression of AMPs, mainly Drosomycin. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Fungal-infected Spn1 null mutants exhibit an up-regulation in Drosomycin (Fullaondo et al., 2011). Surprisingly, none of these genes are classified as canonical immune genes (Chapman et al., 2020). First, forward genetics in flies can identify novel genes that also have relevance to human behavior. Google Scholar. 1, 135145. 2008;105:203927. PubMed doi: 10.1128/IAI.01212-10, Sderhll, K., and Cerenius, L. (1998). J Insect Physiol. doi: 10.1038/nature07712. Immunol. Comparative validation of the D. melanogaster modENCODE transcriptome annotation. Epidemiology and etiology. For SZ, working memory or sensorimotor gating deficits such as prepulse inhibition and habituation are such endophenotypes. Genetic and genome-wide RNAi screens in either intact flies or cell lines have identified a wide array of host effector molecules and pathways involved in host defense against invading pathogens. In Drosophila, functional data publicized a role of several fruit fly TEPs, including TEP2, TEP3, and TEP6 in binding to several pathogens including E. coli, S. aureus, and C. albicans, respectively (Stroschein-Stevenson et al., 2006). The role of quorum sensing in the pathogenicity of the cunning aggressor Pseudomonas aeruginosa. Entomol. Trends Microbiol. doi: 10.1159/000248649, Lacy, D. B., and Collier, R. J. Refined LexA transactivators and their use in combination with the Drosophila Gal4 system. FASEB J. Translational approaches in neuropsychopharmacology using Drosophila. Rab7, CG8743, and the ESCRT machinery, for instance, represent unique vulnerability factors of the host cell, as manipulating any of these factors alone no longer constrains the growth of the non-pathogen Mycobacterium smegmatis in Drosophila (Yang et al., 2015). U.S.A. 105, 1596715972. Alcohol Clin Exp Res 37: 18621871. Drosophila melanogaster has been a popular model organism since the early 20th century, when Thomas H. Morgan first used the organism in the study of heredity. Examples for each of these approaches are cited in the text. This tolerance is an adaptation in the nervous system, and thus called functional tolerance, and not a change in the kinetics of ethanol absorption and metabolism (Scholz et al, 2000). Sci. Cell 127: 199211. Baehrecke EH. doi: 10.1016/S0092-8674(04)00173-4, Blaszczyk, J., Tropea, J. E., Bubunenko, M., Routzahn, K. M., Waugh, D. S., Court, D. L., et al. Drosophila, a chief tool in contemporary genetic studies, became one of the most powerful model organisms widely used in scientific explorations. CAS 2010;330:178797. Nature 436, 10401043. (2015). Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. 5, 4861. Genetic screening in the fruit fly revealed additional antiviral roles of DEAD-box helicase. Provided by the Springer Nature SharedIt content-sharing initiative, Neuropsychopharmacology (Neuropsychopharmacol.) PubMed Animal models allow scientists to explore human diseases whilst avoiding. Because this might be similarly hard for the negative symptoms, such as lack of affect, one approach to model this disorder is to focus on mechanistic validity, and to molecularly study a SZ-associated human gene in flies. Iyengar SK, Elston RC (2007). Likewise, Candida glabrata mutant strains lacking the yapsin virulence factors or the high-osmolarity glycerol pathway exhibit a less virulent effect in infected flies (Quintin et al., 2013). EMBO J. P. gingivalis causes systemic infection in Drosophila and promotes potent killing in a dose-dependent manner. At low doses, flies show locomotor activation (Wolf et al, 2002) and disinhibition (Lee et al, 2008), whereas higher doses lead to loss of righting reflex and sedation (Rodan et al, 2002). Immunol. During the second stage of encapsulation, the number of circulating hemocytes increases for a short term, and lamellocytes differentiate from plasmatocytes (Rizki and Rizki, 1990). Strikingly, Gottar et al. ModSP, a modular serine protease, activates the Toll pathway to culminate in AMP production. doi: 10.1016/S0092-8674(01)00267-7, Li, H., Li, W. X., and Ding, S. W. (2002). https://doi.org/10.1038/npp.2015.322, DOI: https://doi.org/10.1038/npp.2015.322. Melanization is also involved in wound healing, phagocytosis, blood coagulation, and AMP expression in arthropods (Ashida and Brey, 1995; Sderhll and Cerenius, 1998; Cerenius et al., 2008). Remarkably, this bactericidal activity of -hexosaminidase seems to be Mycobacterium marinum specific, as it is not involved in constraining the growth of other bacterial species like Salmonella typhimurium and Listeria monocytogenes (Koo et al., 2008). BMC Genomics 16:519. doi: 10.1186/s12864-015-1690-2, Castillo, J. C., Shokal, U., and Eleftherianos, I. Nat Biotechnol. doi: 10.1016/j.immuni.2009.02.009, Shiratsuchi, A., Mori, T., Sakurai, K., Nagaosa, K., Sekimizu, K., Lee, B. L., et al. Mol. Rev. Several studies also highlighted a role of PGRPs in inducing melanization. cadherins. Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. 1906;23:153. PLoS Biol. Biogr Mem Natl Acad Sci. After the pathogen deposits on the host cell surface (1), it binds to phagocytic receptors and gets internalized (2) and enclosed in a membrane-bound vacuole forming a phagosome (3). Cell 131: 391404. Cuttell, et al. 2009;37:142337. Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan, You can also search for this author in doi: 10.1534/genetics.114.162289, Schmidt, R. L., Trejo, T. R., Plummer, T. B., Platt, J. L., and Tang, A. H. (2007). Insect Biochem. The genetic basis of complex traits: rare variants or "common gene, common disease"? Brand, A. H., and Perrimon, N. (1993). In addition, as flies will continue to believe that they can fly, we might increasingly understand not just the how but even the why. Shift in ribonucleotide reductase gene expression in Pseudomonas aeruginosa during infection. Toll-like receptors and innate immunity. doi: 10.1016/j.molimm.2010.05.012, Benghezal, M., Fauvarque, M. O., Tournebize, R., Froquet, R., Marchetti, A., Bergeret, E., et al. Prepulse inhibition of the Tritonia escape swim. Cell Host Microbe 5, 200211. Cell 104, 709718. Since the IMD pathway is similar to the mammalian tumor necrosis factor receptor (TNFR) pathway (Leulier et al., 2000; Costa et al., 2009), which plays a critical role in infectious disease control particularly against viral infections (Herbein and O'Brien, 2000), several studies deployed Drosophila as a model organism to gain further insight into the role of IMD signaling in anti-viral immunity. It is mainly activated upon microbial infection and/or cellular damage induced by stress response/pathogen infection, and culminates in the production of regulatory molecules, anti-viral agents, and anti-bacterial agents including AMPs. The history of the Drosophila model in the study of various aspects of life sciences will be summarized in this chapter. Dis. Nat. 197, 479486. Boley N, Stoiber MH, Booth BW, Wan KH, Hoskins RA, et al. PLoS ONE 12:e0172071. Gilford Nh School Closing, Articles D