A Mechanosensory Pathway to the
            <i>Drosophila</i>
            Circadian Clock

Simoni, Alekos; Wolfgang, Werner; Topping, Matthew P; Kavlie, Ryan G.; Stanewsky, Ralf; Albert, Joerg T.

doi:10.1126/science.1245710

Cited by 67 publications

(76 citation statements)

References 35 publications

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“…For example, improving systemic time cues, such as regular meal times, or periodic warming of the affected joint, may be useful approaches to minimize or correct age-related loss of circadian function. Of note is that the circadian system in flies has been identified as mechanosensitive 56,108 . If mechanical stimulation can re-entrain the joint clock (either directly or indirectly through the brain), perhaps a regular daily schedule of gentle exercise 109,110 would benefit local joint rhythms.…”

Section: Discussionmentioning

confidence: 99%

The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond

Bérenbaum

Meng

2016

Nat Rev Rheumatol

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Osteoarthritis (OA) is a prevalent and debilitating joint disease for which ageing, obesity and chronic inflammation are known risk factors. The central, peripheral and autonomic nervous systems are essential in all metabolic systems, and emerging evidence suggests a role for these systems in OA. In the past few years, metabolic diseases, such as obesity or diabetes, have been linked to disruption of circadian rhythms that are tightly regulated by the nervous system, whereas inflammatory and autoimmune diseases are known to be linked to disruption of the cholinergic vagus nerve reflex. Interestingly, metabolism, inflammation and circadian rhythms have all been linked to the development and progression of OA. This article reviews current knowledge of the direct and indirect roles of the nervous system and circadian system in the initiation and/or progression of OA, and highlights the directions for future research in this emerging field.

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Section: Discussionmentioning

confidence: 99%

The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond

Bérenbaum

Meng

2016

Nat Rev Rheumatol

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“…of zeitgebers that entrain animal clocks in a more complex and natural context, but also show that non-photic time givers may override photic entrainment [107][108][109].…”

Section: Converging Key Concepts Of Both Fields: Plasticity and Chronmentioning

confidence: 94%

Two sides of a coin: ecological and chronobiological perspectives of timing in the wild

Helm

Visser

Schwartz

et al. 2017

Phil. Trans. R. Soc. B

143

199

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Most processes within organisms, and most interactions between organisms and their environment, have distinct time profiles. The temporal coordination of such processes is crucial across levels of biological organization, but disciplines differ widely in their approaches to study timing. Such differences are accentuated between ecologists, who are centrally concerned with a holistic view of an organism in relation to its external environment, and chronobiologists, who emphasize internal timekeeping within an organism and the mechanisms of its adjustment to the environment. We argue that ecological and chronobiological perspectives are complementary, and that studies at the intersection will enable both fields to jointly overcome obstacles that currently hinder progress. However, to achieve this integration, we first have to cross some conceptual barriers, clarifying prohibitively inaccessible terminologies. We critically assess main assumptions and concepts in either field, as well as their common interests. Both approaches intersect in their need to understand the extent and regulation of temporal plasticity, and in the concept of 'chronotype', i.e. the characteristic temporal properties of individuals which are the targets of natural and sexual selection. We then highlight promising developments, point out open questions, acknowledge difficulties and propose directions for further integration of ecological and chronobiological perspectives through Wild Clock research.

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“…To calculate the phase of the main activity peaks after DD and TC involving genotypes that did not show clear activity peaks during entrainment, we employed circular phase plot analysis as previously described 40,41 . In brief, the mean activity phase of the 3 consecutive days after release into constant conditions was determined for each fly of the two genotypes to be compared.…”

Section: Behavioural Analysismentioning

confidence: 99%

Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature

Chen

Buhl

et al. 2015

Nature

Self Cite

165

177

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Summary:Circadian clocks are endogenous timers adjusting behaviour and physiology with the solar day 1 .Synchronized circadian clocks improve fitness 2 and are crucial for our physical and mental wellbeing 3 . Visual and non-visual photoreceptors are responsible for synchronizing circadian clocks to light 4,5 , but clock-resetting is also achieved by alternating day and night temperatures with only 2°-4°C difference [6][7][8] . This temperature sensitivity is remarkable considering that the circadian clock period (~24 h) is largely independent of surrounding ambient temperatures 1,8 .Here we show that Drosophila Ionotropic Receptor 25a (IR25a) is required for behavioural synchronization to low-amplitude temperature cycles. This channel is expressed in sensory neurons of internal stretch receptors previously implicated in temperature synchronization of the circadian clock 9 . IR25a is required for temperature-synchronized clock protein oscillations in subsets of central clock neurons. Extracellular leg nerve recordings reveal temperature -and IR25a-dependent sensory responses, and IR25a mis-expression confers temperature-dependent firing of heterologous neurons. We propose that IR25a is part of an input pathway to the circadian clock that detects small temperature differences. This pathway operates in the absence of known 'hot' and 'cold' sensors in the Drosophila antenna 10,11 , revealing the existence of novel periphery-to-brain temperature signalling channels. Main Text:In Drosophila, daily activity rhythms are controlled by a network of ~150 clock neurons expressing the clock genes period (per) and timeless (tim). These encode repressor proteins that 3 negatively feedback on their own promoters resulting in 24 h oscillations of clock molecules.Temperature cycles (TC) synchronise molecular clocks present in peripheral appendages in a tissue-autonomous manner 9,12 , while synchronization of clock neurons in the brain largely depends on peripheral temperature receptors located in the chordotonal organs (ChO) and the ChO-expressed gene nocte 9,12,13 .To discover novel factors involved in temperature entrainment, we identified NOCTEinteracting proteins by co-immunoprecipitation and mass-spectrometry (Extended Data Tab. 1) 14 . We focused on IR25a, a member of a divergent subfamily of ionotropic glutamate receptors and verified the interaction by co-immunoprecipitation after overexpressing IR25a and NOCTE in all clock cells using tim-gal4 (Extended Data Fig. 1a). IR25a is expressed in different populations of sensory neurons, including those in the antenna and labellum [15][16][17] . In the olfactory system IR25a acts as a co-receptor with different odour-sensing IRs 15 .To investigate if IR25a is co-expressed with nocte in ChO we analysed IR25a expression in femur and antennal ChO using an IR25a-gal4 line 15 (Extended Data Fig. 2a). IR25a-gal4 driven mCD8-GFP labelled subsets of ChO neurons in the femur, overlapping substantially with nompC-QF driven QUAS-Tomato signals (Fig. 1 a-c). nompC-QF is expressed in larv...

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A Mechanosensory Pathway to the Drosophila Circadian Clock

Cited by 67 publications

References 35 publications

The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond

The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond

Two sides of a coin: ecological and chronobiological perspectives of timing in the wild

Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature

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