Neuropeptide F signaling regulates parasitoid-specific germline development and egg-laying in Drosophila

Autoři: Madhumala K. Sadanandappa aff001;  Shivaprasad H. Sathyanarayana aff001;  Shu Kondo aff002;  Giovanni Bosco aff001
Působiště autorů: Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America aff001;  Invertebrate Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan aff002
Vyšlo v časopise: Neuropeptide F signaling regulates parasitoid-specific germline development and egg-laying in Drosophila. PLoS Genet 17(3): e1009456. doi:10.1371/journal.pgen.1009456
Kategorie: Research Article


Drosophila larvae and pupae are at high risk of parasitoid infection in nature. To circumvent parasitic stress, fruit flies have developed various survival strategies, including cellular and behavioral defenses. We show that adult Drosophila females exposed to the parasitic wasps, Leptopilina boulardi, decrease their total egg-lay by deploying at least two strategies: Retention of fully developed follicles reduces the number of eggs laid, while induction of caspase-mediated apoptosis eliminates the vitellogenic follicles. These reproductive defense strategies require both visual and olfactory cues, but not the MB247-positive mushroom body neuronal function, suggesting a novel mode of sensory integration mediates reduced egg-laying in the presence of a parasitoid. We further show that neuropeptide F (NPF) signaling is necessary for both retaining matured follicles and activating apoptosis in vitellogenic follicles. Whereas previous studies have found that gut-derived NPF controls germ stem cell proliferation, we show that sensory-induced changes in germ cell development specifically require brain-derived NPF signaling, which recruits a subset of NPFR-expressing cell-types that control follicle development and retention. Importantly, we found that reduced egg-lay behavior is specific to parasitic wasps that infect the developing Drosophila larvae, but not the pupae. Our findings demonstrate that female fruit flies use multimodal sensory integration and neuroendocrine signaling via NPF to engage in parasite-specific cellular and behavioral survival strategies.

Klíčová slova:

Behavior – Drosophila melanogaster – Eggs – Larvae – Ovaries – Parasitic diseases – RNA interference – Wasps


1. Inglis GD, Johnson DL, Goettel MS. Effects of Temperature and Thermoregulation on Mycosis byBeauveria bassianain Grasshoppers. Biol Control. 1996;7: 131–139. doi: 10.1006/bcon.1996.0076

2. Parker BJ, Elderd BD, Dwyer G. Host behaviour and exposure risk in an insect-pathogen interaction. J Anim Ecol. 2010. doi: 10.1111/j.1365-2656.2010.01690.x 20384645

3. Parker BJ, Spragg CJ, Altincicek B, Gerardo NM. Symbiont-Mediated Protection against Fungal Pathogens in Pea Aphids: a Role for Pathogen Specificity? Appl Environ Microbiol. 2013;79: 2455–2458. doi: 10.1128/AEM.03193-12 23354709

4. Singer MS, Mace KC, Bernays EA. Self-Medication as Adaptive Plasticity: Increased Ingestion of Plant Toxins by Parasitized Caterpillars. May RC, editor. PLoS One. 2009;4: e4796. doi: 10.1371/journal.pone.0004796 19274098

5. Bozler J, Kacsoh BZ, Bosco G. Transgenerational inheritance of ethanol preference is caused by maternal NPF repression. Elife. 2019;8. doi: 10.7554/eLife.45391 31287057

6. Lefèvre T, Oliver L, Hunter MD, De Roode JC. Evidence for trans-generational medication in nature. Ecol Lett. 2010;13: 1485–1493. doi: 10.1111/j.1461-0248.2010.01537.x 21040353

7. Lefèvre T, Chiang A, Kelavkar M, Li H, Li J, de Castillejo CLF, et al. Behavioural resistance against a protozoan parasite in the monarch butterfly. J Anim Ecol. 2012;81: 70–79. doi: 10.1111/j.1365-2656.2011.01901.x 21939438

8. Fleury F, Ris N, Allemand R, Fouillet P, Carton Y, Boulétreau M. Ecological and Genetic Interactions in Drosophila–parasitoids Communities: A Case Study with D. Melanogaster, D. Simulans and their Common Leptopilina Parasitoids in Southe-astern France. Genetica. 2004;120: 181–194. doi: 10.1023/b:gene.0000017640.78087.9e 15088657

9. Fleury F, Gibert P, Ris N, Allemand R. Chapter 1 Ecology and Life History Evolution of Frugivorous Drosophila Parasitoids. Advances in Parasitology. Academic Press; 2009. pp. 3–44. doi: 10.1016/S0065-308X(09)70001-6

10. Schlenke TA, Morales J, Govind S, Clark AG. Contrasting infection strategies in generalist and specialist wasp parasitoids of Drosophila melanogaster. PLoS Pathog. 2007. doi: 10.1371/journal.ppat.0030158 17967061

11. Carton Y, Nappi AJ. Drosophila cellular immunity against parasitoids. Parasitol Today. 1997;13: 218–227. doi: 10.1016/s0169-4758(97)01058-2 15275074

12. Hwang RY, Zhong L, Xu Y, Johnson T, Zhang F, Deisseroth K, et al. Nociceptive Neurons Protect Drosophila Larvae from Parasitoid Wasps. Curr Biol. 2007;17: 2105–2116. doi: 10.1016/j.cub.2007.11.029 18060782

13. Robertson JL, Tsubouchi A, Tracey WD. Larval Defense against Attack from Parasitoid Wasps Requires Nociceptive Neurons. Skoulakis EMC, editor. PLoS One. 2013;8: e78704. doi: 10.1371/journal.pone.0078704 24205297

14. Ebrahim SAM, Dweck HKM, Stökl J, Hofferberth JE, Trona F, Weniger K, et al. Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit. Benton R, editor. PLOS Biol. 2015;13: e1002318. doi: 10.1371/journal.pbio.1002318 26674493

15. Lynch ZR, Schlenke TA, de Roode JC. Evolution of behavioural and cellular defences against parasitoid wasps in the Drosophila melanogaster subgroup. J Evol Biol. 2016;29: 1016–1029. doi: 10.1111/jeb.12842 26859227

16. Kacsoh BZ, Bozler J, Ramaswami M, Bosco G. Social communication of predator-induced changes in Drosophila behavior and germ line physiology. Elife. 2015;4: e07423. doi: 10.7554/eLife.07423 25970035

17. Kacsoh BZ, Lynch ZR, Mortimer NT, Schlenke TA. Fruit Flies Medicate Offspring After Seeing Parasites. Science (80-). 2013;339: 947–950. doi: 10.1126/science.1229625 23430653

18. Kacsoh BZ, Bozler J, Hodge S, Ramaswami M, Bosco G. A Novel Paradigm for Nonassociative Long-Term Memory in Drosophila: Predator-Induced Changes in Oviposition Behavior. Genetics. 2015;199: 1143–1157. doi: 10.1534/genetics.114.172221 25633088

19. Kacsoh BZ, Schlenke TA. High Hemocyte Load Is Associated with Increased Resistance against Parasitoids in Drosophila suzukii, a Relative of D. melanogaster. DeSalle R, editor. PLoS One. 2012;7: e34721. doi: 10.1371/journal.pone.0034721 22529929

20. Tatevik S, Allison T, Richa A, Eltyeb A, Kristin W. Detecting apoptosis in Drosophila tissues and cells. methods. 2014;68: 89–96. doi: 10.1016/j.ymeth.2014.02.033 24613678

21. McCall K. Eggs over easy: Cell death in the Drosophila ovary. Developmental Biology. Academic Press; 2004. pp. 3–14. doi: 10.1016/j.ydbio.2004.07.017 15355784

22. Spradling AC. Developmental Genetics of Oogenesis. In: Bate M, Martinez-Arias A, editors. The Development of Drosophila melanogaster. Cold Spring Harbor Press; 1993. pp. 1–70.

23. von Lintig J, Dreher A, Kiefer C, Wernet MF, Vogt K. Analysis of the blind Drosophila mutant ninaB identifies the gene encoding the key enzyme for vitamin A formation in vivo. Proc Natl Acad Sci. 2012;98: 1130–1135. doi: 10.1073/pnas.98.3.1130

24. Voolstra O, Oberhauser V, Sumser E, Meyer NE, Maguire ME, Huber A, et al. NinaB is essential for Drosophila vision but induces retinal degeneration in opsin-deficient photoreceptors. J Biol Chem. 2010;285: 2130–2139. doi: 10.1074/jbc.M109.056101 19889630

25. Hardie RC, Raghu P, Moore S, Juusola M, Baines RA, Sweeney ST. Calcium Influx via TRP Channels Is Required to Maintain PIP2 Levels in Drosophila Photoreceptors. Neuron. 2001;30: 149–159. doi: 10.1016/s0896-6273(01)00269-0 11343651

26. Stökl J, Hofferberth J, Pritschet M, Brummer M, Ruther J. Stereoselective chemical defense in the Drosophila parasitoid Leptopilina heterotoma is mediated by (-)-iridomyrmecin and (+)-isoiridomyrmecin. J Chem Ecol. 2012;38: 331–339. doi: 10.1007/s10886-012-0103-0 22477024

27. Weiss I, Rössler T, Hofferberth J, Brummer M, Ruther J, Stökl J. A nonspecific defensive compound evolves into a competition avoidance cue and a female sex pheromone. Nat Commun. 2013;4: 2767. doi: 10.1038/ncomms3767 24231727

28. Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron. 2004;43: 703–714. doi: 10.1016/j.neuron.2004.08.019 15339651

29. Sweeney ST, Broadie K, Keane J, Niemann H, O’Kane CJ. Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Neuron. 1995;14: 341–351. doi: 10.1016/0896-6273(95)90290-2 7857643

30. Martin J-R, Keller A, Sweeney ST. Targeted expression of tetanus toxin: a new tool to study the neurobiology of behavior. Adv Genet. 2002;47: 1–47. doi: 10.1016/s0065-2660(02)47001-0 12000095

31. Couto A, Alenius M, Dickson BJ. Molecular, Anatomical, and Functional Organization of the Drosophila Olfactory System. Curr Biol. 2005;15: 1535–1547. doi: 10.1016/j.cub.2005.07.034 16139208

32. McElvain SM, Bright RD, Johnson PR. The Constituents of the Volatile Oil of Catnip. I. Nepetalic Acid, Nepetalactone and Related Compounds. J Am Chem Soc. 1941;63: 1558–1563. doi: 10.1021/ja01851a019

33. Zhu JJ, Berkebile DR, Dunlap CA, Zhang A, Boxler D, Tangtrakulwanich K, et al. Nepetalactones from essential oil of Nepeta cataria represent a stable fly feeding and oviposition repellent. Med Vet Entomol. 2012;26: 131–138. doi: 10.1111/j.1365-2915.2011.00972.x 21781140

34. Völkl W, Hübner G, Dettner K. Interactions betweenAlloxysta brevis (Hymenoptera, Cynipoidea, Alloxystidae) and honeydew-collecting ants: How an aphid hyperparasitoid overcomes ant aggression by chemical defense. J Chem Ecol. 1994;20: 2901–2915. doi: 10.1007/BF02098397 24241923

35. Chin SG, Maguire SE, Huoviala P, Jefferis GSXE, Potter CJ. Olfactory Neurons and Brain Centers Directing Oviposition Decisions in Drosophila. Cell Rep. 2018;24: 1667–1678. doi: 10.1016/j.celrep.2018.07.018 30089274

36. Stensmyr MC, Dweck HKM, Farhan A, Ibba I, Strutz A, Mukunda L, et al. A Conserved Dedicated Olfactory Circuit for Detecting Harmful Microbes in Drosophila. Cell. 2012;151: 1345–1357. doi: 10.1016/j.cell.2012.09.046 23217715

37. Takemura S, Aso Y, Hige T, Wong A, Lu Z, Xu CS, et al. A connectome of a learning and memory center in the adult Drosophila brain. Elife. 2017;6. doi: 10.7554/eLife.26975 28718765

38. Yagi R, Mabuchi Y, Mizunami M, Tanaka NK. Convergence of multimodal sensory pathways to the mushroom body calyx in Drosophila melanogaster. Sci Rep. 2016;6: 29481. doi: 10.1038/srep29481 27404960

39. Aso Y, Grübel K, Busch S, Friedrich AB, Siwanowicz I, Tanimoto H. The mushroom body of adult Drosophila characterized by GAL4 drivers. J Neurogenet. 2009;23: 156–172. doi: 10.1080/01677060802471718 19140035

40. Nässel DR, Winther ÅME. Drosophila neuropeptides in regulation of physiology and behavior. Progress in Neurobiology. 2010. pp. 42–104. doi: 10.1016/j.pneurobio.2010.04.010 20447440

41. Schoofs L, De Loof A, Van Hiel MB. Neuropeptides as Regulators of Behavior in Insects. Annu Rev Entomol. 2017;62: 35–52. doi: 10.1146/annurev-ento-031616-035500 27813667

42. Nässel DR, Zandawala M. Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior. Prog Neurobiol. 2019;179: 101607. doi: 10.1016/j.pneurobio.2019.02.003 30905728

43. Gendron CM, Kuo T-H, Harvanek ZM, Chung BY, Yew JY, Dierick HA, et al. Drosophila Life Span and Physiology Are Modulated by Sexual Perception and Reward. Science (80-). 2014;343: 544–548. doi: 10.1126/science.1243339 24292624

44. Gendron CM, Chung BY, Pletcher SD. The sensory system: More than just a window to the external world. Commun Integr Biol. 2015;8: e1017159. doi: 10.1080/19420889.2015.1017159 26480026

45. Ameku T, Yoshinari Y, Texada MJ, Kondo S, Amezawa K, Yoshizaki G, et al. Midgut-derived neuropeptide F controls germline stem cell proliferation in a mating-dependent manner. PLoS Biol. 2018;16: e2005004. doi: 10.1371/journal.pbio.2005004 30248087

46. Kondo S, Ueda R. Highly Improved gene targeting by germline-specific Cas9 expression in Drosophila. Genetics. 2013;195: 715–721. doi: 10.1534/genetics.113.156737 24002648

47. Lee G, Bahn JH, Park JH. Sex- and clock-controlled expression of the neuropeptide F gene in Drosophila. Proc Natl Acad Sci. 2006;103: 12580–12585. doi: 10.1073/pnas.0601171103 16894172

48. Wen T, Parrish CA, Xu D, Wu Q, Shen P. Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. Proc Natl Acad Sci. 2005;102: 2141–2146. doi: 10.1073/pnas.0406814102 15677721

49. Chung BY, Ro J, Hutter SA, Miller KM, Guduguntla LS, Kondo S, et al. Drosophila Neuropeptide F Signaling Independently Regulates Feeding and Sleep-Wake Behavior. Cell Rep. 2017;19: 2441–2450. doi: 10.1016/j.celrep.2017.05.085 28636933

50. Veenstra JA, Agricola H-J, Sellami A. Regulatory peptides in fruit fly midgut. Cell Tissue Res. 2008;334: 499–516. doi: 10.1007/s00441-008-0708-3 18972134

51. Song W, Veenstra JA, Perrimon N. Control of Lipid Metabolism by Tachykinin in Drosophila. Cell Rep. 2014;9: 40–47. doi: 10.1016/j.celrep.2014.08.060 25263556

52. Song W, Veenstra JA, Perrimon N. Control of Lipid Metabolism by Tachykinin in Drosophila. Cell Rep. 2020;30: 2461. doi: 10.1016/j.celrep.2020.02.011 32075776

53. Rezával C, Pavlou HJ, Dornan AJ, Chan YB, Kravitz EA, Goodwin SF. Neural circuitry underlying Drosophila female postmating behavioral responses. Curr Biol. 2012;22: 1155–1165. doi: 10.1016/j.cub.2012.04.062 22658598

54. Garczynski SF, Brown MR, Shen P, Murray TF, Crim JW. Characterization of a functional neuropeptide F receptor from Drosophila melanogaster. Peptides. 2002;23: 773–780. doi: 10.1016/s0196-9781(01)00647-7 11897397

55. Hudson AM, Cooley L. Methods for studying oogenesis. Methods. 2014;68: 207–217. doi: 10.1016/j.ymeth.2014.01.005 24440745

56. Lee H, Choi HW, Zhang C, Park Z-Y, Kim Y-J. A Pair of Oviduct-Born Pickpocket Neurons Important for Egg-Laying in Drosophila melanogaster. Mol Cells. 2016;39: 573–579. doi: 10.14348/molcells.2016.0121 27378227

57. Kurz CL, Charroux B, Chaduli D, Viallat-Lieutaud A, Royet J. Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition. Elife. 2017;6: e21937. doi: 10.7554/eLife.21937 28264763

58. Cole SH, Carney GE, McClung CA, Willard SS, Taylor BJ, Hirsh J. Two Functional but Noncomplementing Drosophila Tyrosine Decarboxylase Genes. J Biol Chem. 2005;280: 14948–14955. doi: 10.1074/jbc.M414197200 15691831

59. Grueber WB, Ye B, Yang C-H, Younger S, Borden K, Jan LY, et al. Projections of Drosophila multidendritic neurons in the central nervous system: links with peripheral dendrite morphology. Development. 2007;134: 55–64. doi: 10.1242/dev.02666 17164414

60. Kacsoh BZ, Bozler J, Hodge S, Bosco G. Neural circuitry of social learning in Drosophila requires multiple inputs to facilitate inter-species communication. Commun Biol. 2019;2: 309. doi: 10.1038/s42003-019-0557-5 31428697

61. Pfeiffer BD, Jenett A, Hammonds AS, Ngo T-TB, Misra S, Murphy C, et al. Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci. 2008;105: 9715–9720. doi: 10.1073/pnas.0803697105 18621688

62. Jenett A, Rubin GM, Ngo T-TB, Shepherd D, Murphy C, Dionne H, et al. A GAL4-Driver Line Resource for Drosophila Neurobiology. Cell Rep. 2012;2: 991–1001. doi: 10.1016/j.celrep.2012.09.011 23063364

63. Rizki RM, Rizki TM. Selective destruction of a host blood cell type by a parasitoid wasp. Proc Natl Acad Sci. 1984;81: 6154–6158. doi: 10.1073/pnas.81.19.6154 6435126

64. Rizki TM, Rizki RM, Carton Y. Leptopilina heterotoma and L. boulardi: Strategies to avoid cellular defense responses of Drosophila melanogaster. Exp Parasitol. 1990;70: 466–475. doi: 10.1016/0014-4894(90)90131-u 2108875

65. Ojima N, Hara Y, Ito H, Yamamoto D. Genetic dissection of stress-induced reproductive arrest in Drosophila melanogaster females. Taghert PH, editor. PLOS Genet. 2018;14: e1007434. doi: 10.1371/journal.pgen.1007434 29889831

66. Shohat-Ophir G, Kaun KR, Azanchi R, Mohammed H, Heberlein U. Sexual Deprivation Increases Ethanol Intake in Drosophila. Science (80-). 2012;335: 1351–1355. doi: 10.1126/science.1215932 22422983

67. Sah R, Ekhator NN, Strawn JR, Sallee FR, Baker DG, Horn PS, et al. Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder. Biol Psychiatry. 2009;66: 705–707. doi: 10.1016/j.biopsych.2009.04.037 19576571

68. Thorsell A, Mathé AA. Neuropeptide Y in Alcohol Addiction and Affective Disorders. Front Endocrinol (Lausanne). 2017;8. doi: 10.3389/fendo.2017.00178 28824541

69. Ryu JR, Hong CJ, Kim JY, Kim E-K, Sun W, Yu S-W. Control of adult neurogenesis by programmed cell death in the mammalian brain. Mol Brain. 2016;9: 43. doi: 10.1186/s13041-016-0224-4 27098178

70. Obernier K, Alvarez-Buylla A. Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development. 2019;146: dev156059. doi: 10.1242/dev.156059 30777863

71. Berg DA, Belnoue L, Song H, Simon A. Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development. 2013;140: 2548–2561. doi: 10.1242/dev.088005 23715548

72. Ward EJ, Thaipisuttikul I, Terayama M, French RL, Jackson SM, Cosand KA, et al. GAL4 enhancer trap patterns duringDrosophila development. genesis. 2002;34: 46–50. doi: 10.1002/gene.10138 12324946

73. Manseau L, Baradaran A, Brower D, Budhu A, Elefant F, Phan H, et al. GAL4 enhancer traps expressed in the embryo, larval brain, imaginal discs, and ovary of drosophila. Dev Dyn. 1997;209: 310–322. doi: 10.1002/(SICI)1097-0177(199707)209:3<310::AID-AJA6>3.0.CO;2-L 9215645

74. Duffy JB, Harrison DA, Perrimon N. Identifying loci required for follicular patterning using directed mosaics. Development. 1998;125: 2263–71. Available: 9584125

75. Cabrera GR, Godt D, Fang P-Y, Couderc J-L, Laski FA. Expression pattern of Gal4 enhancer trap insertions into the bric à brac locus generated by P element replacement. genesis. 2002;34: 62–65. doi: 10.1002/gene.10115 12324949

76. Sahai-Hernandez P, Nystul TG. A dynamic population of stromal cells contributes to the follicle stem cell niche in the Drosophila ovary. Development. 2013;140: 4490–4498. doi: 10.1242/dev.098558 24131631

77. Wu JS, Luo L. A protocol for dissecting Drosophila melanogaster brains for live imaging or immunostaining. Nat Protoc. 2006;1: 2110–2115. doi: 10.1038/nprot.2006.336 17487202

78. Micchelli CA. Whole-mount immunostaining of the adult Drosophila gastrointestinal tract. Methods. 2014;68: 273–279. doi: 10.1016/j.ymeth.2014.03.022 24680702

79. Ables ET, Drummond-Barbosa D. The Steroid Hormone Ecdysone Functions with Intrinsic Chromatin Remodeling Factors to Control Female Germline Stem Cells in Drosophila. Cell Stem Cell. 2010;7: 581–592. doi: 10.1016/j.stem.2010.10.001 21040900

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