scholarly journals miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2

2018 ◽  
Author(s):  
Wesley Leigh ◽  
Zhenxing Liu ◽  
Xiaoge Nian ◽  
Yong Zhang

AbstractCircadian clocks control the timing of animal behavior rhythms to anticipate daily environmental changes. Fruit flies gradually increase their activity and reach a peak of activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3’ UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO and Fas2ΔmiR-210. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.Author summaryCircadian clocks control the timing of animal physiology. Drosophila has been a powerful model in understanding the mechanisms of circadian regulation. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. Here we identify miR-210 as a critical regulator of evening anticipatory behavior. Depletion of miR-210 in flies advances evening anticipation. Futhermore, we identify the cell adhesion molecular Fas2 as miR-210’s target in circadian regulation. Fas2 abundance is increased in fly brain lacking of miR-210. Using CRISPR-Cas9 genome editing method, we deleted the miR-210 binding site on 3’ untranslated region of Fas2 and observed similar phenotype as miR-210 mutants. Altogether, our results indicate a novel mechanism of miR-210 in regulation of circadian anticipatory behavior through inhibition of Fas2.

2022 ◽  
Author(s):  
Yanli Xiang ◽  
Thomas Sapir ◽  
Pauline Rouillard ◽  
Marina Ferrand ◽  
Jose M Jimenez-Gomez

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.


2018 ◽  
Author(s):  
Xiaoge Nian ◽  
Wenfeng Chen ◽  
Weiwei Bai ◽  
Zhangwu Zhao ◽  
Yong Zhang

Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In Drosophila , the small ventral lateral neurons (sLNvs) are the master pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here we identified miR-263b as an important regulator of circadian rhythms in Drosophila . Flies depleted of miR-263b ( miR-263b KO ) exhibited dramatically impaired rhythms under constant darkness. Indeed, miR-263b is rhythmically expressed and controls circadian output by affecting the structural plasticity of sLNvs through inhibition of expression of the LIM-only protein Beadex ( Bx ). The misexpression of Bx in flies phenocopied miR-263b KO in behavior and molecular characteristics. In addition, the circadian phenotypes of miR-263b KO were recapitulated by mutating the miR-263b binding sites in the Bx 3′UTR. Together, these results establish miR-263b as an important regulator of circadian locomotor behavior.


2021 ◽  
Author(s):  
Brian A Hodge ◽  
Geoffrey T Meyerhof ◽  
Subhash D Katewa ◽  
Ting Lian ◽  
Charles Lau ◽  
...  

Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in D. melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Disrupting circadian rhythms in the eye by inhibiting the transcription factor, Clock (CLK), or CLK-output genes, accelerated visual senescence, induced a systemic immune response, and shortened lifespan. Flies subjected to dietary restriction were protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extended lifespan in flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicate that vision is an antagonistically pleiotropic process that contributes to organismal aging.


2012 ◽  
Vol 303 (4) ◽  
pp. G461-G473 ◽  
Author(s):  
Jaclyn N. Malloy ◽  
Jiffin K. Paulose ◽  
Ye Li ◽  
Vincent M. Cassone

Circadian clocks are responsible for daily rhythms in a wide array of processes, including gastrointestinal (GI) function. These are vital for normal digestive rhythms and overall health. Previous studies demonstrated circadian clocks within the cells of GI tissue. The present study examines the roles played by the suprachiasmatic nuclei (SCN), master circadian pacemaker for overt circadian rhythms, and the sympathetic nervous system in regulation of circadian GI rhythms in the mouse Mus musculus . Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6-hydroxydopamine has no effect on feeding and locomotor rhythmicity in light-dark cycles or constant darkness but attenuates stool weight and stool number rhythms. Again, however, restricted feeding reestablishes rhythms in locomotor activity, feeding, and stool output rhythms. Ex vivo, intestinal tissue from PER2::LUC transgenic mice expresses circadian rhythms of luciferase bioluminescence. Chemical sympathectomy has little effect on these rhythms, but timed administration of the β-adrenergic agonist isoproterenol causes a phase-dependent shift in PERIOD2 expression rhythms. Collectively, the data suggest that the SCN are required to maintain feeding, locomotor, and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the GI system.


2012 ◽  
Vol 303 (1) ◽  
pp. R8-R18 ◽  
Author(s):  
Reiko Iwadate ◽  
Yoko Satoh ◽  
Yukino Watanabe ◽  
Hiroshi Kawai ◽  
Naomi Kudo ◽  
...  

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (Tb) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1–3 h in terms of the biological rhythms of Tbor LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ∼0.3 h shortening of the period of circadian Tbrhythms in mice kept under conditions of constant darkness ( P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg−1·day−1) or glucose (9 g·kg−1·day−1) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms ( P < 0.05) and restored the decrease of heme ( P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 923 ◽  
Author(s):  
Xiaoge Nian ◽  
Wenfeng Chen ◽  
Weiwei Bai ◽  
Zhangwu Zhao ◽  
Yong Zhang

Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In Drosophila, the small ventral lateral neurons (sLNvs) are primary pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here, we identified miR-263b as an important regulator of circadian rhythms and structural plasticity of sLNvs in Drosophila. Depletion of miR-263b (miR-263bKO) in flies dramatically impaired locomotor rhythms under constant darkness. Indeed, miR-263b is required for the structural plasticity of sLNvs. miR-263b regulates circadian rhythms through inhibition of expression of the LIM-only protein Beadex (Bx). Consistently, overexpression of Bx or loss-of-function mutation (BxhdpR26) phenocopied miR-263bKO and miR-263b overexpression in behavior and molecular characteristics. In addition, mutating the miR-263b binding sites in the Bx 3′ UTR using CRISPR/Cas9 recapitulated the circadian phenotypes of miR-263bKO flies. Together, these results establish miR-263b as an important regulator of circadian locomotor behavior and structural plasticity.


2021 ◽  
Author(s):  
Brian Hodge ◽  
Geoffrey Meyerhof ◽  
Subhash Katewa ◽  
Ting Lian ◽  
Charles Lau ◽  
...  

Abstract Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in D. melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Disrupting circadian rhythms in the eye by inhibiting the transcription factor, Clock (CLK), or CLK-output genes, accelerated visual senescence, induced a systemic immune response, and shortened lifespan. Flies subjected to dietary restriction were protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extended lifespan in flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicate that vision is an antagonistically pleiotropic process that contributes to organismal aging.


2019 ◽  
Author(s):  
Enrique Arboleda ◽  
Martin Zurl ◽  
Kristin Tessmar-Raible

AbstractBackgroundThe marine bristle wormPlatynereis dumeriliiis a useful functional model system for the study of the circadian clock and its interplay with others, e.g. circalunar clocks. The focus has so far been on the worm’s head. However, behavioral and physiological cycles in other animals typically arise from the coordination of circadian clocks located in the brain and in peripheral tissues. Here we focus on peripheral circadian rhythms and clocks, revisit and expand classical circadian work on the worm’s chromatophores, investigate locomotion as read-out and include molecular analyses.ResultsWe establish that different pieces of the trunk exhibit synchronized, robust oscillations of core circadian clock genes. These circadian core clock transcripts are under strong control of the light-dark cycle, quickly losing synchronized oscillation under constant darkness, irrespective of the absence or presence of heads. Different wavelengths are differently effective in controlling the peripheral molecular synchronization. We have previously shown that locomotor activity is under circadian clock control. Here we show that upon decapitation it still follows the light-dark cycle, but does not free-run under constant darkness. We also observe the rhythmicity of pigments in the worm’s individual chromatophores, confirming that chromatophore size changes follow a circadian pattern. These size changes continue under constant darkness, but cannot be re-entrained by light upon decapitation.ConclusionsHere we provide the first basic characterization of the peripheral circadian clock ofPlatynereis dumerilii. In the absence of the head, light is essential as a major synchronization cue for peripheral molecular and locomotor circadian rhythms. Circadian changes in chromatophore size can however continue for several days in the absence of light/dark changes and the head. Thus, the dependence on the head depends on the type of peripheral rhythm studied. These data show that peripheral circadian rhythms and clocks should be considered when investigating the interactions of clocks with different period lengths, a notion likely also true for other organisms with circadian and non-circadian clocks.


2010 ◽  
Vol 109 (5) ◽  
pp. 1328-1336 ◽  
Author(s):  
Ann-Marie Martin ◽  
Jeffrey A. Elliott ◽  
Pat Duffy ◽  
Catriona M. Blake ◽  
Sarra Ben Attia ◽  
...  

Circadian rhythms are innate 24-h cycles in behavioral and biochemical processes that permit physiological anticipation of daily environmental changes. Elucidating the relationship between activity rhythms and circadian patterns of gene expression may contribute to improved human and equine athletic performance. Six healthy, untrained mares were studied to determine whether locomotor activity behavior and skeletal muscle gene expression reflect endogenous circadian regulation. Activity was recorded for three consecutive 48-h periods: as a group at pasture (P), and individually stabled under a light-dark (LD) cycle and in constant darkness (DD). Halter-mounted Actiwatch-L data-loggers recorded light exposure and motor activity. Analysis of mean activity (average counts/min, activity bouts/day, average bout length) and cosinor parameters (acrophase, amplitude, mesor, goodness of fit) revealed a predominantly ultradian (8.9 ± 0.7 bouts/24 h) and weakly circadian pattern of activity in all three conditions (P, LD, DD). A more robust circadian pattern was observed during LD and DD. Muscle biopsies were obtained from the middle gluteal muscles every 4 h for 24 h under DD. One-way qRT-PCR results confirmed the circadian expression ( P < 0.05) of six core clock genes ( Arntl, Per1, Per2, Nr1d1, Nr1d2, Dbp) and the muscle-specific transcript, Myf6. Additional genes, Ucp3, Nrip1, and Vegfa, demonstrated P values approaching significance. These findings demonstrate circadian regulation of muscle function and imply that human management regimes may strengthen, or unmask, equine circadian behavioral outputs. As exercise synchronizes circadian rhythms, our findings provide a basis for future work determining peak times for training and competing horses, to reduce injury and to achieve optimal performance.


2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.


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