Experimental assessment of the network properties of the <i>Drosophila</i> circadian clock

Beckwith, Esteban J.; Ceriani, M. Fernanda

doi:10.1002/cne.23728

Cited by 23 publications

(24 citation statements)

References 56 publications

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“…Notably, the neuropeptide Pigment Dispersing Factor (PDF) is produced by about 10% of the pacemakers (called ventrolateral neurons, LNv, Helfrich-Forster, 1997). PDF mediates pacemaking functions by the LNv neurons (Renn et al , 1999; Beckwith and Ceriani, 2015; Dissel et al , 2014; Yao and Shafer, 2014), but how it does so remains a mystery. PDF signaling promotes molecular cycles among clock cells (Cusumano et al , 2009; Im et al , 2011; Lear et al , 2009; Lin et al , 2004; Peng et al , 2003; Yoshii et al , 2011); it also supports the stability of TIMELESS (Seluzicki et al , 2014) and PER (Li et al , 2014).…”

Section: Introductionmentioning

confidence: 99%

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation

Klose

Duvall

et al. 2016

Neuron

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The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness, does not require endogenous ligand (PDF) signaling, or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additional, cell autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling.

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Section: Introductionmentioning

confidence: 99%

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation

Klose

Duvall

et al. 2016

Neuron

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“…In the absence of PDF, in DD, molecular oscillations in the sLNv subgroup dampen and become asynchronous, while oscillations in other circadian neurons (LNd, DN1 and DN2) become decoupled from sLNv and run with a short period reflected as weak activity rhythms of short period [7,13,14,17,20]. Additional studies suggest complex functions for PDF—drives molecular rhythms in some neuronal groups, synchronises molecular oscillations among certain circadian neuronal groups and shortens or lengthens period in other neuronal groups [15,21–23]. Studies show that loss of behavioural rhythmicity occurs with disruption of PDF oscillations in sLNv DP, suggesting that PDF oscillations are necessary for activity rhythms in DD [16,17,24].…”

Section: Introductionmentioning

confidence: 99%

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness

2017

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In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation.

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“…2a). Based on their anatomical location and specific clock gene expression, these clock neurons can be divided into distinct groups that govern different aspects of circadian behaviors26272829. To map neural loci important for CRTC-dependent circadian behaviors, we examined whether CRTC depletion in specific neurons affected free-running locomotor behaviors.…”

Section: Resultsmentioning

confidence: 99%

CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila

Kim

Lee

Hur

et al. 2016

Sci Rep

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Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species.

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Experimental assessment of the network properties of the Drosophila circadian clock

Cited by 23 publications

References 56 publications

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness

CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila

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