Even a stopped clock tells the right time twice a day: circadian timekeeping in Drosophila

Collins, Ben; Blau, Justin

doi:10.1007/s00424-006-0188-9

Cited by 20 publications

(13 citation statements)

References 88 publications

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“…Temporal delays between activation and repression generate 24-h oscillations in steady-state levels of many clock gene transcripts. Due to reference limitations, we refer the reader to recent reviews covering these topics in detail (3, 5, 6). …”

Section: Molecular Mechanisms Of Drosophila Circadian Clocksmentioning

confidence: 99%

“…Although we provide an overview here, we refer the reader to recent reviews on this subject for more details (3, 6). Light activates CRY, which then binds TIM, targeting it for degradation.…”

Section: Molecular Mechanisms Of Drosophila Circadian Clocksmentioning

confidence: 99%

“…Molecular clocks are located in only ~150 neurons (out of ~250,000) in the Drosophila brain (Figure 4). These neurons are part of a dedicated neural network that drives circadian behavior (please see reviews in References 3, 4, and 6). Distinct subsets of these 150 neurons serve different aspects of circadian behavior, particularly driving wakefulness/locomotor activity at different times of day and under different environmental conditions.…”

Section: A Circadian Pacemaker Neural Network Mediates Distinct Aspecmentioning

confidence: 99%

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Circadian Organization of Behavior and Physiology in Drosophila

Allada

Chung

2010

Annu. Rev. Physiol.

413

435

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Circadian clocks organize behavior and physiology to adapt to daily environmental cycles. Genetic approaches in the fruit fly, Drosophila melanogaster, have revealed widely conserved molecular gears of these 24-h timers. Yet much less is known about how these cell-autonomous clocks confer temporal information to modulate cellular functions. Here we discuss our current knowledge of circadian clock function in Drosophila, providing an overview of the molecular underpinnings of circadian clocks. We then describe the neural network important for circadian rhythms of locomotor activity, including how these molecular clocks might influence neuronal function. Finally, we address a range of behaviors and physiological systems regulated by circadian clocks, including discussion of specific peripheral oscillators and key molecular effectors where they have been described. These studies reveal a remarkable complexity to circadian pathways in this “simple” model organism.

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Section: Molecular Mechanisms Of Drosophila Circadian Clocksmentioning

confidence: 99%

Section: Molecular Mechanisms Of Drosophila Circadian Clocksmentioning

confidence: 99%

Section: A Circadian Pacemaker Neural Network Mediates Distinct Aspecmentioning

confidence: 99%

See 1 more Smart Citation

Circadian Organization of Behavior and Physiology in Drosophila

Allada

Chung

2010

Annu. Rev. Physiol.

413

435

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“…The insect model has been developed most forcefully in Drosophila melanogaster, where two cycling proteins, PERIOD (PER) and TIMELESS (TIM), act as negative regulators of their own transcription through the positively acting bHLH-PAS transcription factors CLOCK (CLK) and CYCLE (CYC, also known as BMAL1) (Hall 2003;Collins and Blau 2007). The CLK protein also cycles and its regulation is interlocked with that of PER, in that CLK/CYC also activate PDP1e and VRILLE (VRI), with the latter modulating expression of Clk (Cyran et al 2003;Benito et al 2007).…”

mentioning

confidence: 99%

Circadian Rhythm Gene Regulation in the Housefly Musca domestica

et al. 2007

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The circadian mechanism appears remarkably conserved between Drosophila and mammals, with basic underlying negative and positive feedback loops, cycling gene products, and temporally regulated nuclear transport involving a few key proteins. One of these negative regulators is PERIOD, which in Drosophila shows very similar temporal and spatial regulation to TIMELESS. Surprisingly, we observe that in the housefly, Musca domestica, PER does not cycle in Western blots of head extracts, in contrast to the TIM protein. Furthermore, immunocytochemical (ICC) localization using enzymatic staining procedures reveals that PER is not localized to the nucleus of any neurons within the brain at any circadian time, as recently observed for several nondipteran insects. However, with confocal analysis, immunofluorescence reveals a very different picture and provides an initial comparison of PER/TIM-containing cells in Musca and Drosophila, which shows some significant differences, but many similarities. Thus, even in closely related Diptera, there is considerable evolutionary flexibility in the number and spatial organization of clock cells and, indeed, in the expression patterns of clock products in these cells, although the underlying framework is similar.

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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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Even a stopped clock tells the right time twice a day: circadian timekeeping in Drosophila

Cited by 20 publications

References 88 publications

Circadian Organization of Behavior and Physiology in Drosophila

Circadian Organization of Behavior and Physiology in Drosophila

Circadian Rhythm Gene Regulation in the Housefly Musca domestica

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

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