Regulation of Feeding and Metabolism by Neuronal and Peripheral Clocks in Drosophila

Xu, Kanyan; Zheng, X. Long; Sehgal, Amita

doi:10.1016/j.cmet.2008.09.006

Cited by 263 publications

(353 citation statements)

References 45 publications

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“…the presence of a functional circadian clock in that tissue, as has recently also been shown by Xu et al (18). We have found that in wild-type, Takeout protein cycling closely follows RNA cycling under LD conditions, as has previously been described (25).…”

Section: Discussionsupporting

confidence: 66%

“…This might be due to limited disruption of the circadian clock in the surviving flies. It has recently been demonstrated that flies that express dnCLK in the fat body driven by a takeout-Gal4 (toGal4) driver (28), which is adult-specific, survive and show a disrupted circadian clock in the fat body (18). We therefore repeated the courtship experiments using to-Gal4 to express UAS-dnClk.…”

Section: Resultsmentioning

confidence: 99%

“…Under LD conditions, a small amount of protein is induced in the mutant at the beginning of the day, again suggesting that protein levels can be directly controlled by light. Control by light in addition to the circadian clock has also been observed for fat body regulated feeding rhythms (18).…”

Section: Discussionmentioning

confidence: 99%

“…Although locomotor activity is the best-characterized circadian output, the circadian clock regulates numerous other outputs such as sleep (13)(14)(15)(16), neuronal activity in olfactory neurons (17), and metabolism (18), and a number of tissues have been found to harbor autonomous clocks (19). This poses the question of the nature of the output genes that mediate these processes.…”

mentioning

confidence: 99%

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The circadian output gene takeout is regulated by Pdp1ε

Benito

Hoxha

Lama

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The circadian clock controls many circadian outputs. Although a large number of transcripts are affected by the circadian oscillator, very little is known about their regulation and function. We show here that the Drosophila takeout gene, one of the output genes of the circadian oscillator, is regulated similarly to the circadian clock genes Clock (Clk) and cry. takeout RNA levels are at constant high levels in Clk JRK mutants. The circadian transcription factor PAR domain protein 1 (Pdp1ε) is a transcription factor that had previously been postulated to control clock output genes, particularly genes regulated similarly to Clk. In agreement with this, we show here that Pdp1ε is a regulator of takeout. Takeout levels are low in flies with reduced Pdp1ε and high in flies with increased amounts of Pdp1ε. Furthermore, flies with reduced or elevated Pdp1ε levels in the fat body display courtship defects, identifying Pdp1ε as an important transcriptional regulator in that tissue.fat body | courtship | clock | Drosophila G enetic and molecular analyses have yielded significant insight into the genes that constitute the core components of the Drosophila circadian clock (reviewed in refs. 1-3). It is regulated by two interlocked transcription/translation-based feedback loops, the period/timeless (per/tim) and Clock (Clk) loops (4). In addition, the regulation of the nuclear entry of proteins, their degradation rate, and phosphorylation state are crucial regulatory steps that are controlled by and contribute to the circadian clock. The per/tim cycle starts with the binding of CLK/CYC heterodimers to E-box promoter elements of the per and tim genes and their subsequent transcriptional activation. Eventually, the newly formed PER and TIM proteins will enter the nucleus and inhibit CLK/CYC action, thereby inhibiting the transcription of their own genes (5-7). Transcription of per and tim will resume once their protein levels have decreased sufficiently to release the inhibition of CLK/CYC. Rhythmic expression of Clock mRNA is regulated in the second loop, the Clock loop. CLK/CYC activate vrille (vri) and Pdp1ε, a transcriptional repressor and activator respectively, that have been shown to bind the Clock promoter competitively (8, 9). Although it was thought that this competition accounts for the oscillatory regulation of Clk mRNA, the fact that Clk mRNA levels are still high in Clk JRK mutants (4) and that the core oscillator is only minimally impacted in flies with increased or decreased PAR domain protein 1 (Pdp1ε) levels (depending on the allele/transgene and tissue examined) (10-12), indicate that an as yet unknown activator is required for Clk transcription. It has recently been demonstrated that CLK protein levels are constant in cells and that it is the phosphorylation state of the protein that determines its binding to DNA and its transcriptional activator function (7).Although locomotor activity is the best-characterized circadian output, the circadian clock regulates numerous other outputs such as sleep (13-16), n...

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Section: Discussionsupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The circadian output gene takeout is regulated by Pdp1ε

Benito

Hoxha

Lama

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…It is not clear however if the changes in these genes have a direct influence on the increase in cold tolerance or if changes of the expression levels of these genes affect changes to the circadian rhythms of the fly in anticipation of the change in seasonal photoperiod. Further functional genetic studies will allow disentanglement of these hypothesis but given extensive work showing how the clock genes have a large influence on the regulation of metabolic processes in Drosophila (Xu et al, 2008;Xu et al, 2011;Sahar and SassoneCorsi, 2012) we suggest that clock genes are good candidates for orchestrating the shifts in metabolic profile seen during cold acclimation.…”

Section: Functional Processesmentioning

confidence: 99%

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

et al. 2015

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For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.

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Roles of peripheral clocks: lessons from the fly

Yildirim¹,

Curtis

Hwangbo

2021

FEBS Letters

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To adapt to and anticipate rhythmic changes in the environment such as daily light-dark and temperature cycles, internal timekeeping mechanisms called biological clocks evolved in a diverse set of organisms, from unicellular bacteria to humans. These biological clocks play critical roles in organisms' fitness and survival by temporally aligning physiological and behavioral processes to the external cues. The central clock is located in a small subset of neurons in the brain and drives daily activity rhythms, whereas most peripheral tissues harbor their own clock systems, which generate metabolic and physiological rhythms. Since the discovery of Drosophila melanogaster clock mutants in the early 1970s, the fruit fly has become an extensively studied model organism to investigate the mechanism and functions of circadian clocks. In this review, we primarily focus on D. melanogaster to survey key discoveries and progresses made over the past two decades in our understanding of peripheral clocks. We discuss physiological roles and molecular mechanisms of peripheral clocks in several different peripheral tissues of the fly.

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Regulation of Feeding and Metabolism by Neuronal and Peripheral Clocks in Drosophila

Cited by 263 publications

References 45 publications

The circadian output gene takeout is regulated by Pdp1ε

The circadian output gene takeout is regulated by Pdp1ε

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

Roles of peripheral clocks: lessons from the fly

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