Genomes and Genes
Gene Symbol: upd3
Description: unpaired 3
Alias: CG15062, CG15062/CG5963, CG33542, CG5963, Dmel\CG33542, UPD3, Upd-3, Upd-like, Upd3, cg15062, cg5963, odsy, upd-3, unpaired 3, CG33542-PB, Unpaired3, outstretched, outstretched-smalleye, small-eye, unpaired, unpaired 3beta, unpaired-3, unpaired-like protein 3, upd homolog, upd3-PB
Species: fruit fly
- Karpowicz P, Perez J, Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development. 2010;137:4135-45 pubmed publisher..These findings demonstrate a cell-autonomous role for the Hippo pathway in SCs, and have implications for understanding the role of this pathway in tumorigenesis and cancer stem cells. ..
- Kuraishi T, Binggeli O, Opota O, Buchon N, Lemaitre B. Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2011;108:15966-71 pubmed publisher..Collectively, our analysis of the dcy immune phenotype indicates that the PM plays an important role in Drosophila host defense against enteric pathogens, preventing the damaging action of pore-forming toxins on intestinal cells. ..
- Ren F, Wang B, Yue T, Yun E, Ip Y, Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A. 2010;107:21064-9 pubmed publisher..Finally, we show that the Hpo pathway mediator Yorkie (Yki) is also required in precursor cells for injury-induced ISC proliferation in response to tissue-damaging reagent DSS. ..
- Jung S, Evans C, Uemura C, Banerjee U. The Drosophila lymph gland as a developmental model of hematopoiesis. Development. 2005;132:2521-33 pubmed..The cellular events identified in this analysis further establish Drosophila as a model system for hematopoiesis. ..
- Hombr a J, Brown S, H der S, Zeidler M. Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. Dev Biol. 2005;288:420-33 pubmed publisher..we describe our analysis of the only invertebrate JAK/STAT pathway ligands identified to date, the Drosophila unpaired-like family...
- Paredes J, Welchman D, Poidevin M, Lemaitre B. Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity. 2011;35:770-9 pubmed publisher..Analysis of the immune phenotype of flies lacking all catalytic PGRPs and the Imd regulator Pirk reveals that the Imd-mediated immune response is highly constrained by the existence of multiple negative feedbacks. ..
- Harrison D, McCoon P, Binari R, Gilman M, Perrimon N. Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. Genes Dev. 1998;12:3252-63 pubmed..We have characterized the unpaired (upd) gene, which displays the same distinctive embryonic mutant defects as mutations in the Drosophila JAK (..
- Rivas M, Cobreros L, Zeidler M, Hombria J. Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences. EMBO Rep. 2008;9:1114-20 pubmed publisher..Our results indicate that the ancestral STAT protein had the capacity to bind to 3n and 4n sites and that specific STAT binding preferences evolved with the radiation of the vertebrate STAT family. ..
- Opota O, Vallet Gely I, Vincentelli R, Kellenberger C, Iacovache I, Gonzalez M, et al. Monalysin, a novel ß-pore-forming toxin from the Drosophila pathogen Pseudomonas entomophila, contributes to host intestinal damage and lethality. PLoS Pathog. 2011;7:e1002259 pubmed publisher..Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis. ..
- Cordero J, Stefanatos R, Myant K, Vidal M, Sansom O. Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the Drosophila adult midgut. Development. 2012;139:4524-35 pubmed publisher..Loss of Apc1 or high Wg in ISCs results in non-cell-autonomous upregulation of upd3 in enterocytes and subsequent activation of Jak/Stat signaling in ISCs...
- Gilbert M, Weaver B, Gergen J, Reich N. A novel functional activator of the Drosophila JAK/STAT pathway, unpaired2, is revealed by an in vivo reporter of pathway activation. Mech Dev. 2005;122:939-48 pubmed..This reporter system will benefit future investigations of JAK/STAT signaling modulators both in whole animals and tissue culture. ..
- Shaw R, Kohlmaier A, Polesello C, Veelken C, Edgar B, Tapon N. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development. 2010;137:4147-58 pubmed publisher..Our results suggest that the Hpo pathway is a mediator of the regenerative response in the Drosophila midgut. ..
- Buchon N, Broderick N, Kuraishi T, Lemaitre B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol. 2010;8:152 pubmed publisher..We show that one signaling pathway, the EGFR pathway, is central to all these stages, and its activation at multiple steps could synchronize the complex cellular events leading to gut repair and homeostasis. ..
- Osman D, Buchon N, Chakrabarti S, Huang Y, Su W, Poidevin M, et al. Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division. J Cell Sci. 2012;125:5944-9 pubmed publisher..Three ligands, Unpaired 1, Unpaired 2 and Unpaired 3 (Upd1, Upd2 and Upd3, respectively) are known to activate the JAK/STAT pathway in Drosophila...
- Lee K, Kim S, Kim E, Ha E, You H, Kim B, et al. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell. 2013;153:797-811 pubmed publisher..These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions. ..
- Buchon N, Broderick N, Chakrabarti S, Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 2009;23:2333-44 pubmed publisher..Altogether, these results indicate that gut homeostasis is achieved by a complex interregulation of the immune response, gut microbiota, and stem cell activity...
- Pastor Pareja J, Wu M, Xu T. An innate immune response of blood cells to tumors and tissue damage in Drosophila. Dis Model Mech. 2008;1:144-54; discussion 153 pubmed publisher..Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans. ..
- Jiang H, Patel P, Kohlmaier A, Grenley M, McEwen D, Edgar B. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;137:1343-55 pubmed publisher..subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division...
- Wright V, Vogt K, Smythe E, Zeidler M. Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cell Signal. 2011;23:920-7 pubmed publisher..By contrast, the Drosophila genome encodes for only three related JAK/STAT ligands, Upd, Upd2 and Upd3. Identifying the differences between these three ligands will ultimately lead to a greater understanding of this ..
- Hombria J, Brown S. The fertile field of Drosophila Jak/STAT signalling. Curr Biol. 2002;12:R569-75 pubmed..Drosophila's streamlined pathway offers a simple model to find new elements and analyse the function of existing ones. ..
- Shin S, Kim S, You H, Kim B, Kim A, Lee K, et al. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science. 2011;334:670-4 pubmed publisher..Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH...
- Zhou F, Rasmussen A, Lee S, Agaisse H. The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment. Dev Biol. 2013;373:383-93 pubmed publisher..Here, we demonstrate the critical role of the UPD3 cytokine in the JAK/STAT-dependent response to enteric infection...
- Wang Y, Huang M. Reduction of Lobe leads to TORC1 hypoactivation that induces ectopic Jak/STAT signaling to impair Drosophila eye development. Mech Dev. 2009;126:781-90 pubmed publisher..L level, by hypomorphic L mutation or heterozygosity of the null L mutation, resulted in ectopic expression of unpaired (upd), which is known to act through the Jak/STAT signal pathway to promote proliferation during eye development...
- Sotillos S, Espinosa Vázquez J, Foglia F, Hu N, Hombria J. An efficient approach to isolate STAT regulated enhancers uncovers STAT92E fundamental role in Drosophila tracheal development. Dev Biol. 2010;340:571-82 pubmed publisher..Our results indicate that vvl and trh are independently activated by STAT92E which is the most important transcription factor required for trachea specification. ..
- You H, Lee W, Lee W. Homeostasis between gut-associated microorganisms and the immune system in Drosophila. Curr Opin Immunol. 2014;30:48-53 pubmed publisher..A deeper understanding of the role of uracil in Drosophila immunity will provide additional insight into the molecular mechanisms underlying host-microbe symbiosis and dysbiosis. ..
- Classen A, Bunker B, Harvey K, Vaccari T, Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet. 2009;41:1150-5 pubmed publisher..in mutant tissue; activation is driven by transcriptional upregulation of Unpaired (Upd, also known as Outstretched, Os) family ligands...
- SantabÃ¡rbara Ruiz P, LÃ³pez SantillÃ¡n M, MartÃnez RodrÃguez I, Binagui Casas A, PÃ©rez L, MilÃ¡n M, et al. ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration. PLoS Genet. 2015;11:e1005595 pubmed publisher..The activation of JNK and p38 results in the expression of the cytokines Unpaired (Upd), which triggers the JAK/STAT signaling pathway required for regeneration...
- Shapiro Kulnane L, Smolko A, SALZ H. Maintenance of Drosophila germline stem cell sexual identity in oogenesis and tumorigenesis. Development. 2015;142:1073-82 pubmed publisher..Our work reveals that GSCs must maintain their sexual identity as they are reprogrammed into a differentiated cell, or risk tumorigenesis. ..
- Hultmark D, Ekengren S. A cytokine in the Drosophila stress response. Dev Cell. 2003;5:360-1 pubmed..However, in this issue of Developmental Cell, show that cytokines do play a role in mediating an acute phase response in this organism. ..
- Wawersik M, Milutinovich A, Casper A, Matunis E, Williams B, Van Doren M. Somatic control of germline sexual development is mediated by the JAK/STAT pathway. Nature. 2005;436:563-7 pubmed..The somatic gonad expresses a JAK/STAT ligand, unpaired (upd), in a male-specific manner, and activates the JAK/STAT pathway in male germ cells at the time of gonad ..
- Fisher K, Stec W, Brown S, Zeidler M. Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran. Mol Biol Cell. 2016;27:434-41 pubmed publisher..Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. ..
- Malagoli D, Sacchi S, Ottaviani E. unpaired (upd)-3 expression and other immune-related functions are stimulated by interleukin-8 in Drosophila melanogaster SL2 cell line. Cytokine. 2008;44:269-74 pubmed publisher..e. cytokines). In Drosophila melanogaster, the cytokine Unpaired (Upd)-3, is known to activate the JAK/STAT pathway, but it is still not clear which molecules and pathways are ..
- Kelsey E, Luo X, Brückner K, Jasper H. Schnurri regulates hemocyte function to promote tissue recovery after DNA damage. J Cell Sci. 2012;125:1393-400 pubmed publisher..Our results identify a new Shn-regulated paracrine signaling interaction between damaged retinal cells and hemocytes that ensures recovery and homeostasis of the challenged tissue. ..
- Bangi E. Drosophila at the intersection of infection, inflammation, and cancer. Front Cell Infect Microbiol. 2013;3:103 pubmed publisher..In this review, I discuss recent advances made by using Drosophila models of cancer to study the role of innate immune pathways Toll/Imd, JNK, and JAK-STAT, microbial infection and inflammation during tumor progression. ..
- Oldefest M, Nowinski J, Hung C, Neelsen D, Trad A, Tholey A, et al. Upd3--an ancestor of the four-helix bundle cytokines. Biochem Biophys Res Commun. 2013;436:66-72 pubmed publisherThe unpaired-like protein 3 (Upd3) is one of the three cytokines of Drosophila melanogaster supposed to activate the JAK/STAT signaling pathway (Janus tyrosine kinases/signal transducer and activator of transcription)...
- Woodcock K, Kierdorf K, Pouchelon C, Vivancos V, Dionne M, Geissmann F. Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet. Immunity. 2015;42:133-44 pubmed..Drosophila macrophages produced the JAK-STAT-activating cytokine upd3, in a scavenger-receptor (crq) and JNK-dependent manner...
- Hill Burns E, Clark A. X-linked variation in immune response in Drosophila melanogaster. Genetics. 2009;183:1477-91 pubmed publisher..Many of the associations act in a sex-specific or sexually antagonistic manner, supporting the theory that with the selective pressures facing genes on the X chromosome, sexually antagonistic variation may be more easily maintained. ..
- Wang L, Ryoo H, Qi Y, Jasper H. PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress. PLoS Genet. 2015;11:e1005220 pubmed publisher..Our studies highlight the significance of the PERK branch of the unfolded protein response of the ER (UPRER) in intestinal homeostasis and provide a viable strategy to improve organismal health- and lifespan. ..
- Sinha A, Khadilkar R, S V, Roychowdhury Sinha A, Inamdar M. Conserved regulation of the Jak/STAT pathway by the endosomal protein asrij maintains stem cell potency. Cell Rep. 2013;4:649-58 pubmed publisher..Thus, Asrij provides a key point of control for spatial and kinetic regulation of stem cell signals. ..
- Housden B, Perrimon N. Spatial and temporal organization of signaling pathways. Trends Biochem Sci. 2014;39:457-64 pubmed publisher..We consider the role of spatial and temporal aspects of different transduction pathways and then discuss how recently developed tools and approaches are helping to dissect the complex mechanisms linking pathway stimulation to output. ..
- Huang X, Shi L, Cao J, He F, Li R, Zhang Y, et al. The sterile 20-like kinase tao controls tissue homeostasis by regulating the hippo pathway in Drosophila adult midgut. J Genet Genomics. 2014;41:429-38 pubmed publisher..Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control. ..
- Markstein M, Dettorre S, Cho J, Neumüller R, Craig Müller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc Natl Acad Sci U S A. 2014;111:4530-5 pubmed publisher..An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence. ..
- Wang L, Sexton T, Venard C, Giedt M, Guo Q, Chen Q, et al. Pleiotropy of the Drosophila JAK pathway cytokine Unpaired 3 in development and aging. Dev Biol. 2014;395:218-31 pubmed publisher..The outstretched wing and small eye phenotypes resemble classical alleles referred to as outstretched (os) mutations that have ..
- Fernandes V, Pradhan Sundd T, Blaquiere J, Verheyen E. Ras/MEK/MAPK-mediated regulation of heparin sulphate proteoglycans promotes retinal fate in the Drosophila eye-antennal disc. Dev Biol. 2015;402:109-18 pubmed publisher..Indeed, STAT activity is reduced due to decreased mobility of the ligand Unpaired (Upd) along with a corresponding loss in Dally-like protein (Dlp), a heparan sulphate proteoglycan (HSPG) that ..
- Zhou J, Florescu S, Boettcher A, Luo L, Dutta D, Kerr G, et al. Dpp/Gbb signaling is required for normal intestinal regeneration during infection. Dev Biol. 2015;399:189-203 pubmed publisher..Our results suggest that Dpp/BMP signaling plays an important role in EBs to maintain tissue integrity and homeostasis during pathogenic infections. ..
- Kux K, Pitsouli C. Tissue communication in regenerative inflammatory signaling: lessons from the fly gut. Front Cell Infect Microbiol. 2014;4:49 pubmed publisher..Here we review tissue communication during homeostasis and regenerative inflammatory signaling in Drosophila focusing on the signals that emanate from non-intestinal epithelial tissues to ensure intestinal integrity. ..
- Brown S, Zeidler M, Hombría J. JAK/STAT signalling in Drosophila controls cell motility during germ cell migration. Dev Dyn. 2006;235:958-66 pubmed..Interestingly, activation of the JAK/STAT pathway is required for these filopodia to form, and ectopic JAK/STAT activation enhances their formation. ..
- Chakrabarti S, Dudzic J, Li X, Collas E, Boquete J, Lemaitre B. Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila. PLoS Genet. 2016;12:e1006089 pubmed publisher..It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3...
- Li Q, Li S, Mana Capelli S, Roth Flach R, Danai L, Amcheslavsky A, et al. The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Dev Cell. 2014;31:291-304 pubmed publisher..Misshapen restricts intestinal stem cell division by repressing the expression of the JAK-STAT pathway ligand Upd3 in differentiating enteroblasts...
- Buchon N, Osman D. All for one and one for all: Regionalization of the Drosophila intestine. Insect Biochem Mol Biol. 2015;67:2-8 pubmed publisher..Further characterization of the gene regulatory networks underlying gut compartmentalization will pave the way for a better understanding of gastrointestinal function in insects and mammals, in both health and disease conditions. ..
- López Onieva L, Fernández Miñán A, González Reyes A. Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary. Development. 2008;135:533-40 pubmed publisher..Our results provide strong evidence for a model in which Jak/Stat signalling in somatic support cells regulates dpp transcription to define niche size and to maintain the adjacent germline stem cells in an undifferentiated state. ..
- Sorrentino R, Melk J, Govind S. Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila. Genetics. 2004;166:1343-56 pubmed
- Bausek N, Zeidler M. G?73B is a downstream effector of JAK/STAT signalling and a regulator of Rho1 in Drosophila haematopoiesis. J Cell Sci. 2014;127:101-10 pubmed publisher..As such, we suggest a mechanism by which JAK/STAT pathway signalling may promote metastasis. ..
- Kolahgar G, Suijkerbuijk S, Kucinski I, Poirier E, Mansour S, Simons B, et al. Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner. Dev Cell. 2015;34:297-309 pubmed publisher..Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic JNK stress signaling.
- Avila F, Erickson J. Drosophila JAK/STAT pathway reveals distinct initiation and reinforcement steps in early transcription of Sxl. Curr Biol. 2007;17:643-8 pubmed..Most XSEs encode transcription factors that bind SxlPe, but the XSE unpaired (upd) encodes a secreted ligand for the JAK/STAT pathway [5-7]...
- Houtz P, Bonfini A, Liu X, Revah J, Guillou A, Poidevin M, et al. Hippo, TGF-?, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection. PLoS Genet. 2017;13:e1007091 pubmed publisher..In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates ..
- Wells R, Barry J, Warrington S, Cuhlmann S, Evans P, Huber W, et al. Control of tissue morphology by Fasciclin III-mediated intercellular adhesion. Development. 2013;140:3858-68 pubmed publisher..Taken together, these results identify a conserved molecular mechanism that directly links JAK/STAT pathway signalling to intercellular adhesion and that sculpts both tubular and planar epithelial shape. ..
- Feng S, Huang J, Wang J. Loss of the Polycomb group gene polyhomeotic induces non-autonomous cell overproliferation. EMBO Rep. 2011;12:157-63 pubmed publisher..We propose that PcG misregulation promotes tumorigenesis through several cellular mechanisms. ..