Genes That Act Downstream of Sensory Neurons to Influence Longevity, Dauer Formation, and Pathogen Responses in
The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.
Vyšlo v časopise:
Genes That Act Downstream of Sensory Neurons to Influence Longevity, Dauer Formation, and Pathogen Responses in. PLoS Genet 8(12): e32767. doi:10.1371/journal.pgen.1003133
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003133
Souhrn
The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.
Zdroje
1. InglisPN, OuG, LerouxMR, ScholeyJM (2007) The sensory cilia of Caenorhabditis elegans. WormBook 1–22.
2. AilionM, ThomasJH (2000) Dauer formation induced by high temperatures in Caenorhabditis elegans. Genetics 156: 1047–1067.
3. ApfeldJ, KenyonC (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402: 804–809.
4. BargmannCI, HorvitzHR (1991) Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251: 1243–1246.
5. GagliaMM, KenyonC (2009) Stimulation of movement in a quiescent, hibernation-like form of Caenorhabditis elegans by dopamine signaling. J Neurosci 29: 7302–7314.
6. AlcedoJ, KenyonC (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41: 45–55.
7. JeongDE, ArtanM, SeoK, LeeSJ (2012) Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front Genet 3: 218.
8. LeeSJ, KenyonC (2009) Regulation of the longevity response to temperature by thermosensory neurons in Caenorhabditis elegans. Curr Biol 19: 715–722.
9. ReddyKC, AndersenEC, KruglyakL, KimDH (2009) A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans. Science 323: 382–384.
10. ShiversRP, KooistraT, ChuSW, PaganoDJ, KimDH (2009) Tissue-specific activities of an immune signaling module regulate physiological responses to pathogenic and nutritional bacteria in C. elegans. Cell Host Microbe 6: 321–330.
11. StyerKL, SinghV, MacoskoE, SteeleSE, BargmannCI, et al. (2008) Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 322: 460–464.
12. SunJ, SinghV, Kajino-SakamotoR, AballayA (2011) Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332: 729–732.
13. ZhangY, LuH, BargmannCI (2005) Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438: 179–184.
14. GarsinDA, VillanuevaJM, BegunJ, KimDH, SifriCD, et al. (2003) Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300: 1921.
15. LinK, HsinH, LibinaN, KenyonC (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28: 139–145.
16. VowelsJJ, ThomasJH (1992) Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. Genetics 130: 105–123.
17. BellLR, StoneS, YochemJ, ShawJE, HermanRK (2006) The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1. Genetics 173: 1275–1286.
18. PerkinsLA, HedgecockEM, ThomsonJN, CulottiJG (1986) Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol 117: 456–487.
19. WangJ, SchwartzHT, BarrMM (2010) Functional specialization of sensory cilia by an RFX transcription factor isoform. Genetics 186: 1295–1307.
20. HaycraftCJ, SwobodaP, TaulmanPD, ThomasJH, YoderBK (2001) The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms. Development 128: 1493–1505.
21. QinH, RosenbaumJL, BarrMM (2001) An autosomal recessive polycystic kidney disease gene homolog is involved in intraflagellar transport in C. elegans ciliated sensory neurons. Curr Biol 11: 457–461.
22. PauliF, LiuY, KimYA, ChenPJ, KimSK (2006) Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans. Development 133: 287–295.
23. Von StetinaSE, WatsonJD, FoxRM, OlszewskiKL, SpencerWC, et al. (2007) Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system. Genome Biol 8: R135.
24. KimSK, LundJ, KiralyM, DukeK, JiangM, et al. (2001) A gene expression map for Caenorhabditis elegans. Science 293: 2087–2092.
25. SchinkelAH (1997) The physiological function of drug-transporting P-glycoproteins. Semin Cancer Biol 8: 161–170.
26. ShepsJA, RalphS, ZhaoZ, BaillieDL, LingV (2004) The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes. Genome Biol 5: R15.
27. KurzCL, ShapiraM, ChenK, BaillieDL, TanMW (2007) Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. Biochem Biophys Res Commun 363: 438–443.
28. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57.
29. Huang daW, ShermanBT, LempickiRA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1–13.
30. FisherAL, LithgowGJ (2006) The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms. Aging Cell 5: 127–138.
31. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277–283.
32. ShapiraM, HamlinBJ, RongJ, ChenK, RonenM, et al. (2006) A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci U S A 103: 14086–14091.
33. TroemelER, ChuSW, ReinkeV, LeeSS, AusubelFM, et al. (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2: e183 doi:10.1371/journal.pgen.0020183.
34. LeeSJ, MurphyCT, KenyonC (2009) Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 10: 379–391.
35. McElweeJJ, SchusterE, BlancE, ThomasJH, GemsD (2004) Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279: 44533–44543.
36. ShostakY, Van GilstMR, AntebiA, YamamotoKR (2004) Identification of C. elegans DAF-12-binding sites, response elements, and target genes. Genes Dev 18: 2529–2544.
37. GerischB, WeitzelC, Kober-EisermannC, RottiersV, AntebiA (2001) A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev Cell 1: 841–851.
38. HsinH, KenyonC (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399: 362–366.
39. KomatsuH, MoriI, RheeJS, AkaikeN, OhshimaY (1996) Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans. Neuron 17: 707–718.
40. HarringtonDP, FlemingTR (1982) A class of rank test procedures for censored survival data. Biometrika 69: 553–566.
41. TimmonsL, CourtDL, FireA (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263: 103–112.
42. SimmerF, TijstermanM, ParrishS, KoushikaSP, NonetML, et al. (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12: 1317–1319.
43. VergaraIA, MahAK, HuangJC, Tarailo-GraovacM, JohnsenRC, et al. (2009) Polymorphic segmental duplication in the nematode Caenorhabditis elegans. BMC Genomics 10: 329.
44. VisserWE, FriesemaEC, VisserTJ (2011) Minireview: thyroid hormone transporters: the knowns and the unknowns. Mol Endocrinol 25: 1–14.
45. ZinkeI, SchutzCS, KatzenbergerJD, BauerM, PankratzMJ (2002) Nutrient control of gene expression in Drosophila: microarray analysis of starvation and sugar-dependent response. EMBO J 21: 6162–6173.
46. KawliT, TanMW (2008) Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol 9: 1415–1424.
47. CheungBH, Arellano-CarbajalF, RybickiI, de BonoM (2004) Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior. Curr Biol 14: 1105–1111.
48. GrayJM, KarowDS, LuH, ChangAJ, ChangJS, et al. (2004) Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430: 317–322.
49. CoatesJC, de BonoM (2002) Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans. Nature 419: 925–929.
50. AlbertPS, BrownSJ, RiddleDL (1981) Sensory control of dauer larva formation in Caenorhabditis elegans. J Comp Neurol 198: 435–451.
51. GariganD, HsuAL, FraserAG, KamathRS, AhringerJ, et al. (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161: 1101–1112.
52. GemsD, RiddleDL (2000) Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154: 1597–1610.
53. Purves DA, George J., Fitzpatrick, David, Katz, Lawrence C., LaMantia, Anthony-Samuel, McNamara, James O., Williams S. Mark. (2001) Neuroscience. Sunderland (MA): Sinauer Associates, Inc.
54. KappelerL, Filho CdeM, DupontJ, LeneuveP, CerveraP, et al. (2008) Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biol 6: e254 doi:10.1371/journal.pbio.0060254.
55. RisoldPY, ThompsonRH, SwansonLW (1997) The structural organization of connections between hypothalamus and cerebral cortex. Brain Res Brain Res Rev 24: 197–254.
56. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.
57. BaldiP, LongAD (2001) A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes. Bioinformatics 17: 509–519.
58. TaubertS, Van GilstMR, HansenM, YamamotoKR (2006) A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. Genes Dev 20: 1137–1149.
59. LeeSJ, HwangAB, KenyonC (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20: 2131–2136.
60. YangJS, NamHJ, SeoM, HanSK, ChoiY, et al. (2011) OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS ONE 6: e23525 doi:10.1371/journal.pone.0023525.
61. TanMW, RahmeLG, SternbergJA, TompkinsRG, AusubelFM (1999) Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci U S A 96: 2408–2413.
62. LeeET, GoOT (1997) Survival analysis in public health research. Annu Rev Public Health 18: 105–134.
63. PradelE, ZhangY, PujolN, MatsuyamaT, BargmannCI, et al. (2007) Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci U S A 104: 2295–2300.
64. Shaham S, ed. (2006) WormBook: Methods in Cell Biology. In: Community TCeR, editor. Wormbook.
65. KamathRS, FraserAG, DongY, PoulinG, DurbinR, et al. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421: 231–237.
66. RualJF, CeronJ, KorethJ, HaoT, NicotAS, et al. (2004) Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14: 2162–2168.
67. Hunt-NewburyR, ViveirosR, JohnsenR, MahA, AnastasD, et al. (2007) High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS Biol 5: e237 doi:10.1371/journal.pbio.0050237.
68. ZhaoZ, ShepsJA, LingV, FangLL, BaillieDL (2004) Expression analysis of ABC transporters reveals differential functions of tandemly duplicated genes in Caenorhabditis elegans. J Mol Biol 344: 409–417.
69. MeissnerB, RogalskiT, ViveirosR, WarnerA, PlastinoL, et al. (2011) Determining the sub-cellular localization of proteins within Caenorhabditis elegans body wall muscle. PLoS ONE 6: e19937 doi:10.1371/journal.pone.0019937.
70. MochiiM, YoshidaS, MoritaK, KoharaY, UenoN (1999) Identification of transforming growth factor-beta- regulated genes in Caenorhabditis elegans by differential hybridization of arrayed cDNAs. Proc Natl Acad Sci U S A 96: 15020–15025.
71. EstesKA, DunbarTL, PowellJR, AusubelFM, TroemelER (2010) bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans. Proc Natl Acad Sci U S A 107: 2153–2158.
72. HaoY, XuN, BoxAC, SchaeferL, KannanK, et al. (2011) Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex. PLoS Genet 7: e1002065 doi:10.1371/journal.pgen.1002065.
73. ChuDS, LiuH, NixP, WuTF, RalstonEJ, et al. (2006) Sperm chromatin proteomics identifies evolutionarily conserved fertility factors. Nature 443: 101–105.
74. NehrkeK, MelvinJE (2002) The NHX family of Na+-H+ exchangers in Caenorhabditis elegans. J Biol Chem 277: 29036–29044.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 12
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
Najčítanejšie v tomto čísle
- Population Genomics of Sub-Saharan : African Diversity and Non-African Admixture
- Insertion/Deletion Polymorphisms in the Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex
- Mi2β Is Required for γ-Globin Gene Silencing: Temporal Assembly of a GATA-1-FOG-1-Mi2 Repressor Complex in β-YAC Transgenic Mice
- Deciphering the Transcriptional-Regulatory Network of Flocculation in