Daytime colour preference in Drosophila depends on the circadian clock and TRP channels

Nature, Journal Year: 2019, Volume and Issue: 574(7776), P. 108 - 111

Published: Sept. 18, 2019

Language: Английский

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Drosophila as a Model to Study the Relationship Between Sleep, Plasticity, and Memory

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: May 28, 2020

Humans spend nearly a third of their life sleeping, yet, despite decades research the function sleep still remains mystery. Sleep has been linked with various biological systems and functions, including metabolism, immunity, cardiovascular system, cognitive functions. Importantly, appears to be present throughout animal kingdom suggesting that it must provide an evolutionary advantage. Among many possible functions sleep, relationship between cognition received lot support. We have all experienced negative effects associated night deprivation. These can include increased emotional reactivity, poor judgment, deficit in attention, impairment learning memory, obviously increase daytime sleepiness. Furthermore, neurological diseases like Alzheimer's disease often disorder component. In some cases, exacerbate progression disease. Thus, is clear plays important role for brain particular, shown play positive consolidation long-term memory while deprivation negatively impacts memory. behavior adapted individual's need influenced by external internal stimuli. addition being adaptive behavior, also modulate plasticity at level synaptic connections neurons neuronal influences sleep. Understanding how modulated stimuli key question neuroscience. order address this question, several models developed. them, fruit fly Drosophila melanogaster its unparalleled genetics proved extremely valuable. excellent model study complex behaviors, learning, This review describes our current knowledge plasticity, using model.

Language: Английский

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CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(7)

Published: Jan. 25, 2021

Article25 January 2021Open Access Source DataTransparent process CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping Marrit Putker orcid.org/0000-0001-9290-408X MRC Laboratory of Molecular Biology, Cambridge, UK Search for more papers by this author David C S Wong orcid.org/0000-0002-1712-9527 Estere Seinkmane orcid.org/0000-0002-3636-4709 Nina M Rzechorzek orcid.org/0000-0003-3209-5019 Aiwei Zeng orcid.org/0000-0003-0354-2529 Nathaniel P Hoyle Johanna E Chesham orcid.org/0000-0002-8981-2667 Mathew D Edwards orcid.org/0000-0002-3573-0025 Kevin A Feeney orcid.org/0000-0003-3143-818X Robin Fischer Biozentrum Universität, Würzburg, Germany Nicolai Peschel orcid.org/0000-0003-3488-832X Ko-Fan Chen orcid.org/0000-0002-7305-6254 Institute Neurology, University College London, Michael Vanden Oever orcid.org/0000-0002-2725-6300 Faculty Medicine, Imperial Rachel Edgar orcid.org/0000-0002-3348-0851 Christopher Selby Department Biochemistry and Biophysics, North Carolina School Chapel Hill, NC, USA Aziz Sancar orcid.org/0000-0001-6469-4900 John O'Neill Corresponding Author [email protected] orcid.org/0000-0003-2204-6096 Information Putker1, Wong1, Seinkmane1, Rzechorzek1, Zeng1, Hoyle1, Chesham1, Edwards1,6, Feeney1, Fischer2, Peschel2, Chen3,7, Oever4, Edgar4, Selby5, Sancar5 *,1 1MRC 2Biozentrum 3Institute 4Faculty 5Department 6Present address: UCL Sainsbury Wellcome Centre Neural Circuits Behaviour, 7Present Genetics Genome Leicester, *Corresponding author. Tel: +44 7739 729425; E-mail: The EMBO Journal (2021)40:e106745https://doi.org/10.15252/embj.2020106745 PDFDownload PDF article text main figures. Peer ReviewDownload a summary the editorial decision including letters, reviewer comments responses feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Circadian rhythms are pervasive property mammalian cells, tissues behaviour, ensuring physiological adaptation solar time. Models cellular revolve around transcriptional feedback repression, whereby CLOCK BMAL1 activate expression PERIOD (PER) CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins therefore considered essential components clock mechanism, supported behavioural arrhythmicity CRY-deficient (CKO) mice under constant conditions. Challenging interpretation, we find locomotor adult CKO specific environmental conditions PER2 levels when is absent. CRY-less oscillations variable their have shorter periods than wild-type controls. Importantly, classic hallmarks such as temperature compensation period determination CK1δ/ε activity be maintained. In absence CRY-mediated repression rhythmic Per2 transcription, protein sustained several cycles, accompanied variation stability. We suggest that, whereas imparts robustness functionality onto biological clocks, core mechanism post-translational. SYNOPSIS (CRY) central regulators transcription/translation loop. finding that persists, albeit with reduced cells suggests gene determined evolutionarily-conserved post-translational timing mechanisms. dispensable but functions make robust. knockout exhibit rhythmicity abundance component amplified by, does require, transcription. CK1 GSK3 kinases regulate stability CRY. Introduction adaptive advantage conferred on organisms anticipation 24-h cycle day night has selected evolution clocks different molecular forms, present throughout all kingdoms life (Rosbash, 2009; et al, 2012). robust, they "capable performing without failure wide range conditions" (Merriam-Webster Dictionary, 2020). proposed generate daily delayed transcriptional–translational loop (TTFL) consists activating transcription factor complexes containing repressive complexes, BMAL1:CLOCK targets (reviewed Dunlap, 1999; Reppert Weaver, 2002; Takahashi, 2016). Various coupled, non-essential, auxiliary mechanisms thought fine-tune TTFL co-ordinate cell-type-specific temporal organisation programs; best characterised being effected E-box mediated REV-ERBα/β, encoded Nr1d1/2 genes (Preitner Ueda, 2007; Liu 2008; These loops sufficient 2008). CRY1 CRY2 operate semi-redundantly repressors (Ye 2014; Chiou 2016), required nuclear import PER proteins, together indispensable regulation vivo well cultured ex (Kume Sato 2006; 2016; Ode 2017). Certainly, homozygous null Cry1 Cry2 do express rest/activity cycles standard experimental (Thresher 1998; Horst Muijtjens, Vitaterna 1999). hypothalamic suprachiasmatic nucleus (SCN) locus co-ordination behaviour physiology, research over last two decades stressed strong correlation between SCN its (Welsh 2010; Anand 2013). were intrigued observation roughly half organotypic slices prepared from Cry1−/−,Cry2−/− (CRY knockout; CKO) mouse neonates continue ~ 20 h (short period) rhythms, observed using genetically PER2::LUC protein::luciferase fusion reporter (Maywood 2011; Ono 2013b), despite having previously been described arrhythmic (Liu 2007). Moreover, short reported raised birth light (Ono 2013a). As only neonatal vivo, suggested network-level SCN-specific rescue neuronal circuits, desynchronise during post-natal development 2013b). our view, however, these observations difficult reconcile an requirement generation rhythms. Rather, consistent making important contribution rhythm functional outputs, rather per se, recently shown Bmal1 Clock (Landgraf Ray 2020), had both individual (Bunger 2000; DeBruyne This further reports constitutive perturbs abolish (Fan Nangle Recent questioned need enable timekeeping. For example, translation regulated cytosolic through transcription-independent (Lipton 2015), isolated erythrocytes lacking any DNA (O'Neill Reddy, Cho 2014). some species eukaryotic alga prokaryotic cyanobacteria can occur entirely post-translationally (Sweeney Haxo, 1961; Nakajima 2005; Tomita 2011). Whether non-transcriptional other (nucleated) unknown hence relationship TTFL-mediated open question. Here, used mice, widely accepted Ukai-Tadenuma 2016) test whether function remained might begin dissect postulated oscillator or "cytoscillator" (Hastings Results Cell-autonomous Consistent previous observations, found no significant following entrainment 12 h:12 light:dark (LD) (LL). Upon transition darkness (DD) [described stronger zeitgeber (Chen 2008)] expressed bouts consolidated average 17 greater variance WT controls (Figs 1A B, EV1A–C). Fig 1, representative actograms plotted endogenous tau (τ) allow periodic rest–activity readily observed; 24-h-plotted Figs EV1A EV2A. showed significantly amplitude compared (WT) controls, persisted > 2 weeks, possessing residual oscillation entrained (Fig EV2-EV5 Appendix). support accordance longitudinal bioluminescence recordings revealed approximately 40% 1C). line data reports, exhibited 1D). Figure 1. CRY-independent occurs cell-autonomously Representative double-plotted showing wheel-running (yellow shading) thereafter darkness. Note 48 x-axis vs. 32 CKO. Full figure modulo 24 presented EV1A. Mean (± SEM) (n = 4). P-values calculated two-way ANOVA. Longitudinal (black) (red) (RLU; relative units). traces. immortalised lung fibroblasts. Left panel shows raw traces recording, right same detrended moving remove differences baseline expression. Period fibroblast at least 31 experiments ≥ 3 experiment, values ± SEM shown). unpaired t-test Welch correction. Standard deviations differ (F-test: < 0.0001). Download PowerPoint Click here expand figure. EV1. shading indicating lights on) (top) (LL) (bottom) (DD). Top four figures (modulo h). Rhythmic LL DD condition becomes clear plotting 16-h (i.e. LD also 1A. Bottom left, periodograms weeks darkness, either light. second cohort highlights (left, horizontal represents mean, F-test variance); (right) 10) 12) 1 week (mean SEM, 2-way ANOVA Sidak's MCT). Examples independent fibroblasts variability shape Two experiment. Stringent entrainment, e.g. dexamethasone, increases likelihood observing 30% did observe clearly cycles. Despite efforts, many years, unable identify set recording consistently produced forced conclude variables play adequately able control for. Genotyping study. Left: PCR genotyping expected pattern knockout. Right: Western blot analysis whole cell lysates (WCL) probed antibodies against CRY2. Interexperimental comparison Paired means 1F where rhythmic. paired t-test. Intraexperimental replicates) SEM). P-value was Damping rates example EV1E damped sine wave fitting n 106, 109). available online EV2. Entrainment deficiency Timeless-independent Drosophila melanogaster A. 5) cannot 8 h:8 entrain light-dark 5). Equal numbers age-matched male female used. C. dominant zeitgeber, vary contrast, unnatural indicates vivo. Two-way significance multiple comparisons reported; mean. D. Normalised, XLG-luciferase (XLG-LUC; equivalent PER2::LUC) timeless (Timout) flies (detrended SEM; 21, Timout 36). difference y-axis scaling. E. Damped fit (D). (extra sum-of-squares F-test) indicate hypothesis (straight line). F. Significant XLG-LUC flies. t-test, 36. Data information: Lamaze al (2017). Similar behaviourally cycles: https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/year/2015/docId/11914 EV3. post-transcriptionally curve recombinant luciferase determine number molecules. Known concentrations spiked into (non-luciferase containing) lysate reproduce conditions, signal measured 20-s integration time (CP s; counts s). fitted straight (red line, 95% CI). grey dotted lines (linear) area molecules experiment 3A. co-immunoprecipitation samples 3B. (IgG) pulldowns performed peak (determined parallel recordings) technical replicates (A–C). blots mRNA qPCR one 2, mean timeseries preferentially F-test, 0.0321), (ns). co-recording cultures depicted 3C. Detrended Cry1:LUC (MAFs) 4, extra (P 0.0001), could (no P-value). Nr1d1 promoter WT, quadruple Cry1/2-Per1/2 (CPKO) embryonic (MEFs) recorded 32°C, 3, (solid) ±SEM (dashed). (not significant, temperature-compensated 3). Expanded view Per2:LUC show detected C(P)KO MEFs, Zoomed-out version 37°C 3D 32°C EV3E. temperature-compensated, (from h) Nr1d1:LUC demonstrate explain EV4. oscillates assayed puromycin incorporation Cells synchronised harvested every after 10-min pulse (10 µg/ml). Incorporation blotting anti-puromycin antibody. quantified corrected total loading (Coomassie staining). Bioluminescence labelling course genotypes. immunoprecipitation S6K, eIF4a BMAL1. dexamethasone synchronisation, immunoprecipitated. Example (left) SV40::LUC pulsed 10 µM CHX 46 recording. resulting (symbols) one-phase decay (blue Multiple stable basal treated 25 μg/ml allowing turnover inferred signal. panel, decline simple exponential (solid lines) derive half-life each line. Right level reported, F-test). Timing pulses (labelled I-II (cycle 1) b 2)), trace corresponding G H. phases two-tailed Half-life line-fitting cells. EV5. role cytoplasmic presence inhibitor PF670462 (0.3 µM; PF), 5A (A), CHIR99021 (5 CHIR). KL001 (1 µM). respective quantifications CPKO Nr1d1::LUC (0.1 µM) (3 CHIR) (genotype drug interaction effect) reported. explanations account phenotype: (i) explanation: genetic loss compensated network circuits whose sensitive developmental phase small variations slice preparation Evans 2012; 2013b; Tokuda 2015); (ii) cell-intrinsic (or observed) stochastically less counterparts, interneuronal signalling To distinguish possibilities, asked populations fibroblasts, lack specialised neuropeptidergic so case 1E, EV1C D). Across 100 recordings, independently generated (male female), days Again, increased within (F-test 0.0001, 1F, F). results, occurred experiments, assays. there very little occurrence w

Language: Английский

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nocte Is Required for Integrating Light and Temperature Inputs in Circadian Clock Neurons of Drosophila

Current Biology, Journal Year: 2018, Volume and Issue: 28(10), P. 1595 - 1605.e3

Published: May 1, 2018

Language: Английский

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Integration of Circadian Clock Information in the Drosophila Circadian Neuronal Network

Journal of Biological Rhythms, Journal Year: 2021, Volume and Issue: 36(3), P. 203 - 220

Published: March 1, 2021

Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physiology with planetary rhythms. In Drosophila, the core components of clock comprise a transcription/translation feedback loop expressed in seven neuronal clusters brain. Although it is increasingly evident each regulated differently, how these communicate other across circadian network less clear. Here, we review latest evidence describes physical connectivity . Using small ventral lateral neurons as starting point, summarize one may another, highlighting signaling pathways both upstream downstream clocks. We propose additional efforts required to understand temporal information generated neuron integrated circuit regulate rhythmic behavior.

Language: Английский

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A thermometer circuit for hot temperature adjusts Drosophila behavior to persistent heat

Current Biology, Journal Year: 2022, Volume and Issue: 32(18), P. 4079 - 4087.e4

Published: Aug. 17, 2022

Language: Английский

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Altered circadian rhythm, sleep, and rhodopsin 7 –dependent shade preference during diapause in Drosophila melanogaster

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(27)

Published: June 25, 2024

To survive adverse environments, many animals enter a dormant state such as hibernation, dauer, or diapause. Various Drosophila species undergo adult reproductive diapause in response to cool temperatures and/or short day-length. While flies are less active during diapause, it is unclear how environmental conditions affect circadian rhythms and sleep. Here we show that diapause-inducing temperatures, melanogaster exhibit altered activity profiles, including severely reduced morning an advanced evening peak. Consequently, the have single peak at time similar when nondiapausing take siesta. Temperatures ≤15 °C, rather than photoperiod, primarily drive this behavior. At rapidly deep-sleep lacks sleep cycles of higher require high levels stimulation for arousal. Furthermore, 25 prefer siesta shade, preference virtually eliminated 10 °C. Resting shade driven by aversion blue light sensed Rhodopsin 7 outside eyes. Flies °C neuronal markers elevated pressure, increased expression Bruchpilot Ca 2+ R5 ellipsoid body neurons. Therefore, pressure might overcome aversion. Thus, same cause arrest, preserve germline stem cells, extend lifespan, D. prone deep dramatically altered, yet rhythmic, daily patterns.

Language: Английский

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A Detailed Re-Examination of the Period Gene Rescue Experiments Shows That Four to Six Cryptochrome-Positive Posterior Dorsal Clock Neurons (DN_1p) of Drosophila melanogaster Can Control Morning and Evening Activity

Journal of Biological Rhythms, Journal Year: 2024, Volume and Issue: 39(5), P. 463 - 483

Published: July 31, 2024

Animal circadian clocks play a crucial role in regulating behavioral adaptations to daily environmental changes. The fruit fly

Language: Английский

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Regulation of pre-dawn arousal in Drosophila by a pair of trissinergic descending neurons of the visual and circadian networks

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Natural changes in light interact with circadian regulation at promoters to control gene expression in cyanobacteria

eLife, Journal Year: 2017, Volume and Issue: 6

Published: Dec. 14, 2017

The circadian clock interacts with other regulatory pathways to tune physiology predictable daily changes and unexpected environmental fluctuations. However, the complexity of clocks in higher organisms has prevented a clear understanding how natural conditions affect their physiological outputs. Here, we dissect interaction between regulation responses fluctuating light cyanobacterium Synechococcus elongatus. We demonstrate that intensity substantially expression hundreds circadian-clock-controlled genes, many which are involved key steps metabolism. These arise from light-responsive control RNA polymerase recruitment promoters by network transcription factors including RpaA RpaB. Using phenomenological modeling constrained our data, reveal simple principles underlie small number stereotyped dusk genes light.

Language: Английский

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