Adult Circadian Behavior in Requires Developmental Expression of , But Not
Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex.
Vyšlo v časopise:
Adult Circadian Behavior in Requires Developmental Expression of , But Not. PLoS Genet 7(7): e32767. doi:10.1371/journal.pgen.1002167
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002167
Souhrn
Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex.
Zdroje
1. AlladaRChungBY 2010 Circadian organization of behavior and physiology in Drosophila. Annu Rev Physiol 72 605 624
2. ZhangEEKaySA 2010 Clocks not winding down: unravelling circadian networks. Nat Rev Mol Cell Biol 11 764 776
3. AlladaRWhiteNESoWVHallJCRosbashM 1998 A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 93 791 804
4. LimCChungBYPitmanJLMcGillJJPradhanS 2007 Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. 17 1082 1089
5. DarlingtonTKWager-SmithKCerianiMFStaknisDGekakisN 1998 Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science 280 1599 1603
6. RutilaJESuriVLeMSoWVRosbashM 1998 CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Cell 93 805 814
7. MatsumotoAUkai-TadenumaMYamadaRGHoulJUnoKD 2007 A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. 21 1687 1700
8. KadenerSStoleruDMcDonaldMNawatheanPRosbashM 2007 Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. 21 1675 1686
9. BlauJYoungMW 1999 Cycling vrille expression is required for a functional Drosophila clock. Cell 99 661 671
10. KlossBPriceJLSaezLBlauJRothenfluhA 1998 The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon. Cell 94 97 107
11. PriceJLBlauJRothenfluhAAbodeelyMKlossB 1998 double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94 83 95
12. KlossBRothenfluhAYoungMWSaezL 2001 Phosphorylation of period is influenced by cycling physical associations of double-time, period, and timeless in the Drosophila clock. Neuron 30 699 706
13. ZerrDMHallJCRosbashMSiwickiKK 1990 Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila. J Neurosci 10 2749 2762
14. CurtinKDHuangZJRosbashM 1995 Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron 14 365 372
15. LeeCBaeKEderyI 1999 PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. Mol Cell Biol 19 5316 5325
16. ShaferOTRosbashMTrumanJW 2002 Sequential nuclear accumulation of the clock proteins period and timeless in the pacemaker neurons of Drosophila melanogaster. J Neurosci 22 5946 5954
17. GlossopNRHoulJHZhengHNgFSDudekSM 2003 VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator. Neuron 37 249 261
18. EwerJRosbashMHallJC 1988 An inducible promoter fused to the period gene in Drosophila conditionally rescues adult per-mutant arrhythmicity. Nature 333 82 84
19. EwerJHamblen-CoyleMRosbashMHallJC 1990 Requirement for period gene expression in the adult and not during development for locomotor activity rhythms of imaginal Drosophila melanogaster. J Neurogenet 7 31 73
20. McGuireSELePTOsbornAJMatsumotoKDavisRL 2003 Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302 1765 1768
21. BrandAHPerrimonN 1993 Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. 118 401 415
22. KonopkaRJBenzerS 1971 Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A 68 2112 2116
23. YangZSehgalA 2001 Role of molecular oscillations in generating behavioral rhythms in Drosophila. Neuron 29 453 467
24. BaeKLeeCSidoteDChuangKYEderyI 1998 Circadian regulation of a Drosophila homolog of the mammalian Clock gene: PER and TIM function as positive regulators. Mol Cell Biol 18 6142 6151
25. SehgalARothenfluh-HilfikerAHunter-EnsorMChenYMyersMP 1995 Rhythmic expression of timeless: a basis for promoting circadian cycles in period gene autoregulation. Science 270 808 810
26. CyranSABuchsbaumAMReddyKLLinMCGlossopNR 2003 vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell 112 329 341
27. Claridge-ChangAWijnenHNaefFBoothroydCRajewskyN 2001 Circadian regulation of gene expression systems in the Drosophila head. Neuron 32 657 671
28. PriceJLDembinskaMEYoungMWRosbashM 1995 Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless. Embo J 14 4044 4049
29. LinDMGoodmanCS 1994 Ectopic and increased expression of Fasciclin II alters motoneuron growth cone guidance. Neuron 13 507 523
30. TanoueSKrishnanPKrishnanBDryerSEHardinPE 2004 Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila. Curr Biol 14 638 649
31. StoleruDPengYAgostoJRosbashM 2004 Coupled oscillators control morning and evening locomotor behaviour of Drosophila. Nature 431 862 868
32. RennSCParkJHRosbashMHallJCTaghertPH 1999 A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila. Cell 99 791 802
33. ShaferOTTaghertPH 2009 RNA-interference knockdown of Drosophila pigment dispersing factor in neuronal subsets: the anatomical basis of a neuropeptide's circadian functions. PLoS ONE 4 e8298 doi:10.1371/journal.pone.0008298
34. ParkJHHelfrich-ForsterCLeeGLiuLRosbashM 2000 Differential regulation of circadian pacemaker output by separate clock genes in Drosophila. Proc Natl Acad Sci U S A 97 3608 3613
35. HardinPEHallJCRosbashM 1990 Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343 536 540
36. SmithRFKonopkaRJ 1982 Effects of dosage alterations at the per locus on the period of the circadian clock of Drosophila. Molecular & general genetics 185 30 36
37. BayliesMKBargielloTAJacksonFRYoungMW 1987 Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock. Nature 326 390 392
38. MartinekSYoungMW 2000 Specific genetic interference with behavioral rhythms in Drosophila by expression of inverted repeats. Genetics 156 1717 1725
39. MenetJSAbruzziKCDesrochersJRodriguezJRosbashM 2010 Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA. Genes Dev 24 358 367
40. KanekoMParkJHChengYHardinPEHallJC 2000 Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms. J Neurobiol 43 207 233
41. Helfrich-ForsterCShaferOTWulbeckCGrieshaberERiegerD 2007 Development and morphology of the clock-gene-expressing lateral neurons of Drosophila melanogaster. J Comp Neurol 500 47 70
42. LearBCZhangLAlladaR 2009 The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior. PLoS Biol 7 e1000154 doi:10.1371/journal.pbio.1000154
43. FernandezMPBerniJCerianiMF 2008 Circadian remodeling of neuronal circuits involved in rhythmic behavior. PLoS Biol 6 e69 doi:10.1371/journal.pbio.0060069
44. AlladaRKadenerSNandakumarNRosbashM 2003 A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude. Embo J 22 3367 3375
45. PengYStoleruDLevineJDHallJCRosbashM 2003 Drosophila free-running rhythms require intercellular communication. PLoS Biol 1 e13 doi:10.1371/journal.pbio.0000013
46. GrimaBChelotEXiaRRouyerF 2004 Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain. Nature 431 869 873
47. CurrieJGodaTWijnenH 2009 Selective entrainment of the Drosophila circadian clock to daily gradients in environmental temperature. BMC biology 7 49
48. WijnenHNaefFYoungMW 2005 Molecular and statistical tools for circadian transcript profiling. Methods Enzymol 393 341 365
49. BoothroydCEWijnenHNaefFSaezLYoungMW 2007 Integration of light and temperature in the regulation of circadian gene expression in Drosophila. 3 e54
50. SchmittgenTDLivakKJ 2008 Analyzing real-time PCR data by the comparative C(T) method. Nature protocols 3 1101 1108
51. WuJSLuoL 2006 A protocol for dissecting Drosophila melanogaster brains for live imaging or immunostaining. Nature protocols 1 2110 2115
52. StanewskyRFrischBBrandesCHamblen-CoyleMJRosbashM 1997 Temporal and spatial expression patterns of transgenes containing increasing amounts of the Drosophila clock gene period and a lacZ reporter: mapping elements of the PER protein involved in circadian cycling. J Neurosci 17 676 696
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 7
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice
- Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1
- Gene-Based Tests of Association
- Genome-Wide Association Study Identifies as a Susceptibility Gene for Pediatric Asthma in Asian Populations