The Drosophila Circadian Clock Is a Variably Coupled Network of Multiple Peptidergic Units (original) (raw)

The circadian clock network in the brain of different Drosophila species

Journal of Comparative Neurology, 2013

Comparative studies on cellular and molecular clock mechanisms have revealed striking similarities in the organization of the clocks among different animal groups. To gain evolutionary insight into the properties of the clock network within the Drosophila genus, we analyzed sequence identities and similarities of clock protein homologues and immunostained brains of 10 different Drosophila species using antibodies against vrille (VRI), PAR-protein domain1 (PDP1), and cryptochrome (CRY). We found that the clock network of both subgenera Sophophora and Drosophila consists of all lateral and dorsal clock neuron clusters that were previously described in Drosophila melanogaster. Immunostaining against CRY and the neuropeptide pigment-dispersing factor (PDF), however, revealed species-specific differences. All species of the Drosophila subgenus and Rachele Saccon's current address is

Setting the clock – by nature: Circadian rhythm in the fruitfly Drosophila melanogaster

FEBS Letters, 2011

Nowadays humans mainly rely on external, unnatural clocks such as of cell phones and alarm clocks-driven by circuit boards and electricity. Nevertheless, our body is under the control of another timer firmly anchored in our genes. This evolutionary very old biological clock drives most of our physiology and behavior. The genes that control our internal clock are conserved among most living beings. One organism that shares this ancient clock mechanism with us humans is the fruitfly Drosophila melanogaster. Since it turned out that Drosophila is an excellent model, it is no surprise that its clock is very well and intensely investigated. In the following review we want to display an overview of the current understanding of Drosophila's circadian clock.

Heterogeneity of the Peripheral Circadian Systems in Drosophila melanogaster: A Review

Frontiers in physiology, 2016

Circadian rhythms in organisms are involved in many aspects of metabolism, physiology, and behavior. In many animals, these rhythms are produced by the circadian system consisting of a central clock located in the brain and peripheral clocks in various peripheral tissues. The oscillatory machinery and entrainment mechanism of peripheral clocks vary between different tissues and organs. The relationship between the central and peripheral clocks is also tissue-dependent. Here we review the heterogeneous nature of peripheral circadian clocks in the fruit fly Drosophila melanogaster and their dependence on the central clock, and discuss their significance in the temporal organization of physiology in peripheral tissues/organs.

Integration of Circadian Clock Information in the Drosophila Circadian Neuronal Network

Journal of Biological Rhythms

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

Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila

Nature communications, 2017

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals.

A Self-Sustaining, Light-Entrainable Circadian Oscillator in the Drosophila Brain

Current Biology, 2003

negative feedback loop (reviewed in [1]). In flies the most prominent biological rhythm con-Institut fü r Zoologie Lehrstuhl fü r Entwicklungsbiologie trolled by the circadian clock is the rest-activity cycle. Under free-running conditions of constant darkness and 93040 Regensburg Germany constant temperature (DD), this rhythm persists for at least five weeks (e.g., [2]). In stark contrast to these 2 Department of Biology Brandeis University robust behavioral rhythms, studies of clock-gene expression under such free-running conditions revealed a Waltham, Massachusetts 02454 rapid dampening of molecular oscillations within 2-4 days [1]. It is therefore not proven if cycling gene products are required for generating behavioral rhythmicity. Summary Several arguments have been put forward in order to explain the observed discrepancies. (1) Molecular rhythms Background: The circadian clock of Drosophila is able are usually measured after extraction of mRNA or protein to drive behavioral rhythms for many weeks in continufrom many individuals (typically 30-50) at a given time of ous darkness (DD). The endogenous rhythm generator day. Since the internal free-running periods vary slightly is thought to be generated by interlocked molecular between the different animals, this will lead to an overall feedback loops involving circadian transcriptional and amplitude dampening the longer the flies are kept in posttranscriptional regulation of several clock genes, DD (e.g., [3, 4]). (2) Many tissues within one fly contain including period. However, all attempts to demonstrate circadian clocks (e.g., [5, 6]). Without entrainment cues sustained rhythms of clock gene expression in DD have they could internally desynchronize, resulting in damped failed, making it difficult to link the molecular clock modmolecular rhythms when all such tissues are monitored els with the circadian behavioral rhythms. Here we resimultaneously; the same could also apply for the clock stricted expression of a novel period-luciferase transcells within a given tissue. (3) There is a qualitative differgene to certain clock neurons in the Drosophila brain, ence between "pacemaker oscillators" (e.g., those drivpermitting us to monitor reporter gene activity in these ing robust behavioral rhythms) and "peripheral oscillacells in real-time. tors" (e.g., the fly's eyes, in which clock gene expression Results: We show that only a subset of the previously has been analyzed for the majority of chronomolecular described pacemaker neurons is able to sustain PERIOD studies); only bona-fide pacemakers are able to maintain protein oscillations after 5 days in constant darkness. molecular oscillations in DD. Establishment of luciferase In addition, we identified a sustained and autonomous as a real-time reporter gene helped to rule out the first molecular oscillator in a group of clock neurons in the possibility; recordings from individual transgenic perdorsal brain with heretofore unknown function. We luc flies also showed rapid dampening in DD [7]. Tofound that these "dorsal neurons" (DNs) can synchrogether with the finding that isolated Drosophila body nize behavioral rhythms and that light input into these parts and organs contain circadian clocks (e.g., [5, 6, 8, cells involves the blue-light photoreceptor cryptochrome. 9]), this made the second possibility seem likely. But the Conclusions: Our results suggest that the DNs play a fact that transcriptional rhythms in individually cultured prominent role in controlling locomotor behavior when body parts and organs also rapidly dampen in DD favors flies are exposed to natural light-dark cycles. Analysis the third argument [5, 6, 9]. Therefore, true circadian of similar "stable mosaic" transgenes should help to molecular oscillations could be a unique feature of a set reveal the function of the other clock neuronal clusters of brain neurons known to control behavioral rhythmicity within the fly brain. (e.g., [10, 11]). Little is known about the features of molecular oscilla

Drosophila Clock Neurons under Natural Conditions

Journal of Biological Rhythms, 2013

The circadian clock modulates the adaptive daily patterns of physiology and behavior and adjusts these rhythms to seasonal changes. Recent studies of seasonal locomotor activity patterns of wild-type and clock mutant fruit flies in quasi-natural conditions have revealed that these behavioral patterns differ considerably from those observed under standard laboratory conditions. To unravel the molecular features accompanying seasonal adaptation of the clock, we investigated Drosophila's neuronal expression of the canonical clock proteins PERIOD (PER) and TIMELESS (TIM) in nature. We find that the profile of PER dramatically changes in different seasons, whereas that of TIM remains more constant. Unexpectedly, we find that PER and TIM oscillations are decoupled in summer conditions. Moreover, irrespective of season, PER and TIM always peak earlier in the dorsal neurons than in the lateral neurons, suggesting a more rapid molecular oscillation in these cells. We successfully reproduced most of our results under simulated natural conditions in the laboratory and show that although photoperiod is the most important zeitgeber for the molecular clock, the flies' activity pattern is more strongly affected by temperature. Our results are among the first to systematically compare laboratory and natural studies of Drosophila rhythms.

Functional analysis of circadian pacemaker neurons in Drosophila melanogaster

The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006

The molecular mechanisms of circadian rhythms are well known, but how multiple clocks within one organism generate a structured rhythmic output remains a mystery. Many animals show bimodal activity rhythms with morning (M) and evening (E) activity bouts. One long-standing model assumes that two mutually coupled oscillators underlie these bouts and show different sensitivities to light. Three groups of lateral neurons (LN) and three groups of dorsal neurons govern behavioral rhythmicity of Drosophila. Recent data suggest that two groups of the LN (the ventral subset of the small LN cells and the dorsal subset of LN cells) are plausible candidates for the M and E oscillator, respectively. We provide evidence that these neuronal groups respond differently to light and can be completely desynchronized from one another by constant light, leading to two activity components that free-run with different periods. As expected, a long-period component started from the E activity bout. However,...