A circadian output center controlling feeding:Fasting rhythms in Drosophila

English version

Autoři: Austin P. Dreyer ^aff001; Madison M. Martin ^aff001; Carson V. Fulgham ^aff001; Daniel A. Jabr ^aff001; Lei Bai ^aff002; Jennifer Beshel ^aff001; Daniel J. Cavanaugh ^aff001
Působiště autorů: Department of Biology, Loyola University Chicago, Chicago, Illinois, United States of America ^aff001; Penn Chronobiology, Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ^aff002
Vyšlo v časopise: A circadian output center controlling feeding:Fasting rhythms in Drosophila. PLoS Genet 15(11): e1008478. doi:10.1371/journal.pgen.1008478
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1008478

Souhrn

Circadian rhythms allow animals to coordinate behavioral and physiological processes with respect to one another and to synchronize these processes to external environmental cycles. In most animals, circadian rhythms are produced by core clock neurons in the brain that generate and transmit time-of-day signals to downstream tissues, driving overt rhythms. The neuronal pathways controlling clock outputs, however, are not well understood. Furthermore, it is unclear how the central clock modulates multiple distinct circadian outputs. Identifying the cellular components and neuronal circuitry underlying circadian regulation is increasingly recognized as a critical step in the effort to address health pathologies linked to circadian disruption, including heart disease and metabolic disorders. Here, building on the conserved components of circadian and metabolic systems in mammals and Drosophila melanogaster, we used a recently developed feeding monitor to characterize the contribution to circadian feeding rhythms of two key neuronal populations in the Drosophila pars intercerebralis (PI), which is functionally homologous to the mammalian hypothalamus. We demonstrate that thermogenetic manipulations of PI neurons expressing the neuropeptide SIFamide (SIFa) as well as mutations of the SIFa gene degrade feeding:fasting rhythms. In contrast, manipulations of a nearby population of PI neurons that express the Drosophila insulin-like peptides (DILPs) affect total food consumption but leave feeding rhythms intact. The distinct contribution of these two PI cell populations to feeding is accompanied by vastly different neuronal connectivity as determined by trans-Tango synaptic mapping. These results for the first time identify a non-clock cell neuronal population in Drosophila that regulates feeding rhythms and furthermore demonstrate dissociable control of circadian and homeostatic aspects of feeding regulation by molecularly-defined neurons in a putative circadian output hub.

Klíčová slova:

Drosophila melanogaster – Neurons – Chronobiology – Food consumption – Biological locomotion – Circadian rhythms – Circadian oscillators – Cell activation

Zdroje

1. Vaze KM, Sharma VK. On the adaptive significance of circadian clocks for their owners. Chronobiol Int. 2013;30(4):413–33. doi: 10.3109/07420528.2012.754457 23452153.

2. Bass J. Circadian topology of metabolism. Nature. 2012;491(7424):348–56. doi: 10.1038/nature11704 23151577.

3. Roenneberg T, Merrow M. The circadian clock and human health. Curr Biol. 2016;26(10):R432–43. doi: 10.1016/j.cub.2016.04.011 27218855.

4. Mattson MP, Allison DB, Fontana L, Harvie M, Longo VD, Malaisse WJ, et al. Meal frequency and timing in health and disease. Proc Natl Acad Sci. 2014;111(47):16647–53. doi: 10.1073/pnas.1413965111 25404320.

5. Stanewsky R. Genetic analysis of the circadian system in Drosophila melanogaster and mammals. J Neurobiol. 2003;54(1):111–47. doi: 10.1002/neu.10164 12486701.

6. Dubowy C, Sehgal A. Circadian Rhythms and Sleep in Drosophila melanogaster. Genetics. 2017;205(4):1373–97. doi: 10.1534/genetics.115.185157 28360128.

7. Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol. 2010;72:517–49. doi: 10.1146/annurev-physiol-021909-135821 20148687

8. Nitabach MN, Taghert PH. Organization of the Drosophila Circadian Control Circuit. Curr Biol. 2008;18:84–93. doi: 10.1016/j.cub.2007.11.061 18211849.

9. Allada R, Chung BY. Circadian organization of behavior and physiology in Drosophila. Annu Rev Physiol. 2010;72:605–24. doi: 10.1146/annurev-physiol-021909-135815 20148690.

10. Golombek D a, Rosenstein RE. Physiology of Circadian Entrainment. Physiol Rev. 2010;90(3):1063–102. doi: 10.1152/physrev.00009.2009 20664079.

11. de Velasco B, Erclik T, Shy D, Sclafani J, Lipshitz H, McInnes R, et al. Specification and development of the pars intercerebralis and pars lateralis, neuroendocrine command centers in the Drosophila brain. Dev Biol. 2007;302(1):309–23. doi: 10.1016/j.ydbio.2006.09.035 17070515.

12. Cavanaugh DJ, Geratowski JD, Wooltorton JRA, Spaethling JM, Hector CE, Zheng X, et al. Identification of a Circadian Output Circuit for Rest:Activity Rhythms in Drosophila. Cell. 2014;157(3):689–701. doi: 10.1016/j.cell.2014.02.024 24766812

13. Park D, Veenstra JA, Park JH, Taghert PH. Mapping peptidergic cells in Drosophila: Where DIMM fits in. PLoS One. 2008;3(3) doi: 10.1371/journal.pone.0001896 18365028.

14. Bai L, Lee Y, Cavanaugh D, Haynes P, Gutmann DH, Williams JA, et al. A Conserved Circadian Function for the Neurofibromatosis 1 Gene. Cell Rep. 2018;22(13):3416–26. doi: 10.1016/j.celrep.2018.03.014 29590612

15. King AN, Barber AF, Smith AE, Nitabach MN, Cavanaugh DJ, Sehgal A, et al. A Peptidergic Circuit Links the Circadian Clock to Locomotor Activity. Curr Biol. 2017;27(13):1915–27. doi: 10.1016/j.cub.2017.05.089 28669757

16. Cavey M, Collins B, Bertet C, Blau J. Circadian rhythms in neuronal activity propagate through output circuits. Nat Neurosci. 2016;19(4) doi: 10.1038/nn.4263 26928065.

17. Barber AF, Erion R, Holmes TC, Sehgal A. Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin-producing cells. Genes Dev. 2016;30:2596–606. doi: 10.1101/gad.288258.116 27979876.

18. Nässel DR, Vanden Broeck J. Insulin/IGF signaling in Drosophila and other insects: Factors that regulate production, release and post-release action of the insulin-like peptides. Cell Mol Life Sci. 2016;73(2):271–90. doi: 10.1007/s00018-015-2063-3 26472340.

19. Pool AH, Scott K. Feeding regulation in Drosophila. Curr Opin Neurobiol. 2014;29:57–63. doi: 10.1016/j.conb.2014.05.008 24937262.

20. Branch A, Shen P. Central and Peripheral Regulation of Appetite and Food Intake in Drosophila. In: Harris RBS, editor. Boca Raton (FL); 2017. p. 17–38pmid: 28880507.

21. Terhzaz S, Rosay P, Goodwin SF, Veenstra JA. The neuropeptide SIFamide modulates sexual behavior in Drosophila. Biochem Biophys Res Commun. 2007;352(2):305–10. doi: 10.1016/j.bbrc.2006.11.030 17126293.

22. Park S, Sonn JY, Oh Y, Lim C, Choe J. SIFamide and SIFamide receptor defines a novel neuropeptide signaling to promote sleep in Drosophila. Mol Cells. 2014 Apr;37(4):295–301. doi: 10.14348/molcells.2014.2371 24658384

23. Martelli C, Pech U, Kobbenbring S, Wegener C, Martelli C, Pech U, et al. SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila. Cell Rep. 2017;20:464–78. doi: 10.1016/j.celrep.2017.06.043 28700946

24. Ro J, Harvanek ZM, Pletcher SD. FLIC: high-throughput, continuous analysis of feeding behaviors in Drosophila. PLoS One. 2014;9(6):e101107. doi: 10.1371/journal.pone.0101107 24978054.

25. Talay M, Richman EB, Snell NJ, Hartmann GG, Fisher JD, Sorkaç A, et al. Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango. Neuron. 2017;96(4):783–795.e4. doi: 10.1016/j.neuron.2017.10.011 29107518.

26. Rulifson EJ, Kim SK, Nusse R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science (80-). 2002;296(5570):1118–20. doi: 10.1126/science.1070058 12004130.

27. Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, et al. An internal thermal sensor controlling temperature preference in Drosophila. Nature. 2008;454(7201):217–20. doi: 10.1038/nature07001 18548007.

28. Baines R, Uhler JP, Thompson a, Sweeney ST, Bate M. Altered electrical properties in Drosophila neurons developing without synaptic transmission. J Neurosci. 2001;21(5):1523–31. doi: 10.1523/JNEUROSCI.21-05-01523.2001 11222642.

29. McGuire SE, Le PT, Osborn AJ, Matsumoto K, Davis RL. Spatiotemporal Rescue of Memory Dysfunction in Drosophila. Science (80-). 2003;302(5651):1765–8. doi: 10.1126/science.1089035 14657498.

30. White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H. Genetic control of programmed cell death in Drosophila. Science. 1994;264(5159):677–83. doi: 10.1126/science.8171319 8171319

31. Davie K, Janssens J, Koldere D, De Waegeneer M, Pech U, Kreft L, et al. A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain. Cell. 2018;174(4):982–998.e20. doi: 10.1016/j.cell.2018.05.057 29909982.

32. Croset V, Treiber CD, Waddell S. Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics. Elife. 2018;7. doi: 10.7554/eLife.34550 29671739.

33. Perkins LA, Holderbaum L, Tao R, Hu Y, Sopko R, McCall K, et al. The transgenic RNAi project at Harvard medical school: Resources and validation. Genetics. 2015;201(3):843–52. doi: 10.1534/genetics.115.180208 26320097

34. Ja WW, Carvalho GB, Mak EM, de la Rosa NN, Fang AY, Liong JC, et al. Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A. 2007;104(20):8253–6. doi: 10.1073/pnas.0702726104 17494737.

35. Hall KD, Heymsfield SB, Kemnitz JW, Klein S, Schoeller DA, Speakman JR. Energy balance and its components: Implications for body weight regulation. Am J Clin Nutr. 2012;95(4):989–94. doi: 10.3945/ajcn.112.036350 22434603

36. Crocker A, Shahidullah M, Levitan IB, Sehgal A. Identification of a Neural Circuit that Underlies the Effects of Octopamine on Sleep:Wake Behavior. Neuron. 2010;65(5):670–81. doi: 10.1016/j.neuron.2010.01.032 20223202.

37. Rajashekhar KP, Singh RN. Neuroarchitecture of the tritocerebrum of Drosophila melanogaster. J Comp Neurol. 1994;349(4):633–45. doi: 10.1002/cne.903490410 7860793.

38. Nässel DR, Kubrak OI, Liu Y, Luo J, Lushchak O V. Factors that regulate insulin producing cells and their output in drosophila. Front Physiol. 2013;4:1–12. doi: 10.3389/fphys.2013.00001 24062693.

39. Zhang YQ, Rodesch CK, Broadie K. Living synaptic vesicle marker: synaptotagmin-GFP. Genesis. 2002;34(1–2):142–5. doi: 10.1002/gene.10144 12324970.

40. Nicolai LJJ, Ramaekers A, Raemaekers T, Drozdzecki A, Mauss AS, Yan J, et al. Genetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila. Proc Natl Acad Sci U S A. 2010;107(47):20553–8. doi: 10.1073/pnas.1010198107 21059961.

41. Masse NY, Turner GC, Jefferis GSXE. Olfactory Information Processing in Drosophila. Curr Biol. 2009;19(16):R700–713. doi: 10.1016/j.cub.2009.06.026 19706282.

42. McKellar CE. Motor control of fly feeding. J Neurogenet. 2016;30(2):101–11. doi: 10.1080/01677063.2016.1177047 27309215.

43. Deng B, Li Q, Liu X, Cao Y, Li B, Qian Y, Xu R, Mao R, Zhou E, Zhang W, Huang J, Rao Y. Chemoconnectomics: Mapping Chemical Transmission in Drosophila. Neuron. 2019;101(5):876–893. doi: 10.1016/j.neuron.2019.01.045 30799021

44. Bechtold DA, Loudon ASI. Hypothalamic clocks and rhythms in feeding behaviour. Trends Neurosci. 2013;36(2):74–82. doi: 10.1016/j.tins.2012.12.007 23333345.

45. Paschos GK, Ibrahim S, Song W, Kunieda T, Grant G, Reyes TM, et al. Obesity in mice with adipocyte-specific deletion of clock component Arntl. Nat Med. 2012;18(12):1768–77. doi: 10.1038/nm.2979 23142819

46. Liu Z, Huang M, Wu X, Shi G, Xing L, Dong Z, et al. PER1 Phosphorylation Specifies Feeding Rhythm in Mice. 2014;7(5):1509–20. doi: 10.1016/j.celrep.2014.04.032 24857656

47. Xu K, Zheng X, Sehgal A. Regulation of Feeding and Metabolism by Neuronal and Peripheral Clocks in Drosophila. Cell Metab. 2008;8(4):289–300. doi: 10.1016/j.cmet.2008.09.006 18840359.

48. Helfrich-Forster C. The circadian clock in the brain: a structural and functional comparison between mammals and insects. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2004;190(8):601–13. doi: 10.1007/s00359-004-0527-2 15156341.

49. Geminard C, Rulifson EJ, Leopold P. Remote Control of Insulin Secretion by Fat Cells in Drosophila. Cell Metab. 2009;10(3):199–207. doi: 10.1016/j.cmet.2009.08.002 19723496

50. Rajan A, Perrimon N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell. 2012;151(1):123–37. doi: 10.1016/j.cell.2012.08.019 23021220.

51. Ojima N, Hara Y, Ito H, Yamamoto D. Genetic dissection of stress-induced reproductive arrest in Drosophila melanogaster females. PLoS Genet. 2018;14(6):e1007434. doi: 10.1371/journal.pgen.1007434 29889831

52. Gao XJ, Riabinina O, Li J, Potter CJ, Clandinin TR, Luo L. A transcriptional reporter of intracellular Ca(2+) in Drosophila. Nat Neurosci. 2015;18(6):917–25. doi: 10.1038/nn.4016 25961791.

53. Park S, Alfa RW, Topper SM, Kim GES, Kockel L, Kim SK. A Genetic Strategy to Measure Circulating Drosophila Insulin Reveals Genes Regulating Insulin Production and Secretion. PLoS Genet. 2014;10(8) doi: 10.1371/journal.pgen.1004555 25101872.

54. Itskov PM, Ribeiro C. The dilemmas of the gourmet fly: The molecular and neuronal mechanisms of feeding and nutrient decision making in Drosophila. Front Neurosci. 2013;7(7 FEB):1–13. doi: 10.3389/fnins.2013.00012 23407678.

55. Wu Q, Zhang Y, Xu J, Shen P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A. 2005;102(37):13289–94. doi: 10.1073/pnas.0501914102 16150727.

56. Root CM, Ko KI, Jafari A, Wang JW. Presynaptic facilitation by neuropeptide signaling mediates odor-driven food search. Cell. 2011;145(1):133–44. doi: 10.1016/j.cell.2011.02.008 21458672.

57. Erion R, Sehgal A. Regulation of insect behavior via the insulin-signaling pathway. Front Physiol. 2013;4 DEC(December):1–6. doi: 10.3389/fphys.2013.00353 24348428.

58. Liu Y, Luo J, Carlsson MA, Dick RN. Serotonin and Insulin-Like Peptides Modulate Leucokinin-Producing Neurons That Affect Feeding and Water Homeostasis in Drosophila. 2015;(March). doi: 10.1002/cne.23768 25732325

59. Soderberg JAE, Carlsson MA, Nassel DR. Insulin-Producing Cells in the Drosophila Brain also Express Satiety-Inducing Cholecystokinin-Like Peptide, Drosulfakinin. Front Endocrinol (Lausanne). 2012;3:109. doi: 10.3389/fendo.2012.00109 22969751.

60. Cognigni P, Bailey AP, Miguel-Aliaga I. Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis. Cell Metab. 2011;13(1):92–104. doi: 10.1016/j.cmet.2010.12.010 21195352.

61. Sudhakar SR, Varghese J. Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila. bioRxiv 364554; https://doi.org/10.1101/364554

62. Lee K-S, You K-H, Choo J-K, Han Y-M, Yu K. Drosophila short neuropeptide F regulates food intake and body size. J Biol Chem. 2004;279(49):50781–9. doi: 10.1074/jbc.M407842200 15385546.

63. Hentze JL, Carlsson MA, Kondo S, Nässel DR, Rewitz KF. The neuropeptide allatostatin a regulates metabolism and feeding decisions in drosophila. Sci Rep. 2015;30(5):11680. doi: 10.1038/srep11680 26123697.

64. Hergarden AC, Tayler TD, Anderson DJ. Allatostatin-A neurons inhibit feeding behavior in adult Drosophila. Proc Natl Acad Sci. 2012;109(10):3967–72. doi: 10.1073/pnas.1200778109 22345563.

65. Chen W, Shi W, Li L, Zheng Z, Li T, Bai W, et al. Regulation of sleep by the short neuropeptide F (sNPF) in Drosophila melanogaster. Insect Biochem Mol Biol. 2013;43(9):809–19. doi: 10.1016/j.ibmb.2013.06.003 23796436

66. Chen J, Reiher W, Hermann-Luibl C, Sellami A, Cognigni P, Kondo S, et al. Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF. PLoS Genet. 2016;12(9):1–33. doi: 10.1371/journal.pgen.1006346 27689358.

67. Bischof J, Bjorklund M, Furger E, Schertel C, Taipale J, Basler K. A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila. Development. 2013;140(11):2434–42. doi: 10.1242/dev.088757 23637332.

68. Gilestro GF, Cirelli C. pySolo: a complete suite for sleep analysis in Drosophila. Bioinformatics. 2009;25(11):1466–7. doi: 10.1093/bioinformatics/btp237 19369499.

69. Team RC. R: A language and environment for statistical computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing; 2019.