Faculty Opinions recommendation of The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes.

The circadian oscillator in eukaryotes consists of several interlocking feedback loops through which the expression of clock genes is controlled. It is generally assumed that all plant cells contain essentially identical and cell-autonomous multiloop clocks. Here, we show that the circadian clock in the roots of matureArabidopsisplants differs markedly from that in the shoots and that the root clock is synchronized by a photosynthesis-related signal from the shoot. Two of the feedback loops of the plant circadian clock are disengaged in roots, because two key clock components, the transcription factors CCA1 and LHY, are able to inhibit gene expression in shoots but not in roots. Thus, the plant clock is organ-specific but not organ-autonomous.

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The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0813366106 ◽

2009 ◽

Vol 106 (9) ◽

pp. 3519-3524 ◽

Cited By ~ 51

Author(s):

J. A. Mohawk ◽

M. L. Baer ◽

M. Menaker

Keyword(s):

Clock Genes ◽

Circadian Oscillator

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The Circadian Oscillator of the Cerebellum: Triiodothyronine Regulates Clock Gene Expression in Granule Cells in vitro and in the Cerebellum of Neonatal Rats in vivo

Frontiers in Physiology ◽

10.3389/fphys.2021.706433 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tenna Bering ◽

Henrik Hertz ◽

Martin Fredensborg Rath

Keyword(s):

Gene Expression ◽

Clock Gene ◽

Granule Cells ◽

Clock Genes ◽

Circadian Oscillator ◽

Neonatal Rats ◽

Clock Gene Expression ◽

Mixed Gender

The central circadian clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, but an SCN-dependent molecular circadian oscillator is present in the cerebellar cortex. Recent findings suggest that circadian release of corticosterone is capable of driving the circadian oscillator of the rat cerebellum. To determine if additional neuroendocrine signals act to shape cerebellar clock gene expression, we here tested the role of the thyroid hormone triiodothyronine (T3) in regulation of the cerebellar circadian oscillator. In cultured cerebellar granule cells from mixed-gender neonatal rats, T3 treatment affected transcript levels of the clock genes Per2, Arntl, Nr1d1, and Dbp, suggesting that T3 acts directly on granule cells to control the circadian oscillator. We then used two different in vivo protocols to test the role of T3 in adult female rats: Firstly, a single injection of T3 did not influence clock gene expression in the cerebellum. Secondly, we established a surgical rat model combining SCN lesion with a programmable micropump infusing circadian physiological levels of T3; however, rhythmic infusion of T3 did not reestablish differential clock gene expression between day and night in SCN lesioned rats. To test if the effects of T3 observed in vitro were related to the developmental stage, acute injections of T3 were performed in mixed-gender neonatal rats in vivo; this procedure significantly affected cerebellar expression of the clock genes Per1, Per2, Nr1d1, and Dbp. Developmental comparisons showed rhythmic expression of all clock genes analyzed in the cerebellum of adult rats only, whereas T3 responsiveness was limited to neonatal animals. Thus, T3 shapes cerebellar clock gene profiles in early postnatal stages, but it does not represent a systemic circadian regulatory mechanism linking the SCN to the cerebellum throughout life.

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BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

Endocrine Connections ◽

10.1530/ec-18-0377 ◽

2019 ◽

Vol 8 (1) ◽

pp. 57-68 ◽

Cited By ~ 2

Author(s):

Shuhui Ma ◽

Zixu Wang ◽

Jing Cao ◽

Yulan Dong ◽

Yaoxing Chen

Keyword(s):

Circadian Rhythm ◽

Circadian Rhythms ◽

Pineal Gland ◽

Clock Genes ◽

Critical Role ◽

Green Light ◽

Circadian Oscillator ◽

Melatonin Secretion ◽

Expression Levels

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin.

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Rhythmic Release of Corticosterone Induces Circadian Clock Gene Expression in the Cerebellum

Neuroendocrinology ◽

10.1159/000503720 ◽

2019 ◽

Vol 110 (7-8) ◽

pp. 604-615 ◽

Cited By ~ 3

Author(s):

Tenna Bering ◽

Henrik Hertz ◽

Martin Fredensborg Rath

Keyword(s):

Gene Expression ◽

In Situ Hybridization ◽

Glucocorticoid Receptor ◽

Cerebellar Cortex ◽

Clock Gene ◽

Clock Genes ◽

Circadian Oscillator ◽

Male Rats ◽

Clock Gene Expression

Neurons of the cerebellar cortex contain a circadian oscillator, with circadian expression of clock genes being controlled by the master clock of the suprachiasmatic nucleus (SCN). However, the signaling pathway connecting the SCN to the cerebellum is unknown. Glucocorticoids exhibit a prominent SCN-dependent circadian rhythm, and high levels of the glucocorticoid receptor have been reported in the cerebellar cortex; we therefore hypothesized that glucocorticoids may control the rhythmic expression of clock genes in the cerebellar cortex. We here applied a novel methodology by combining the electrolytic lesion of the SCN with implantation of a micropump programmed to release corticosterone in a circadian manner mimicking the endogenous hormone profile. By use of this approach, we were able to restore the corticosterone rhythm in SCN-lesioned male rats. Clock gene expression in the cerebellum was abolished in rats with a lesioned SCN, but exogenous corticosterone restored the daily rhythm in clock gene expression in the cerebellar cortex, as revealed by quantitative real-time PCR and radiochemical in situ hybridization for the detection of the core clock genes Per1, Per2, and Arntl. On the contrary, exogenous hormone did not restore circadian rhythms in body temperature and running activity. RNAscope in situ hybridization further revealed that the glucocorticoid receptor colocalizes with clock gene products in cells of the cerebellar cortex, suggesting that corticosterone exerts its actions by binding directly to receptors in neurons of the cerebellum. However, rhythmic clock gene expression in the cerebellum was also detectable in adrenalectomized rats, indicating that additional control mechanisms exist. These data show that the cerebellar circadian oscillator is influenced by SCN-dependent rhythmic release of corticosterone.

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Temperature-dependent resetting of the molecular circadian oscillator in Drosophila

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.1714 ◽

2014 ◽

Vol 281 (1793) ◽

pp. 20141714 ◽

Cited By ~ 4

Author(s):

Tadahiro Goda ◽

Brandi Sharp ◽

Herman Wijnen

Keyword(s):

Clock Genes ◽

Circadian Oscillator ◽

Temperature Cycle ◽

Temperature Dependent ◽

Phase Adjustment ◽

Period 2 ◽

Wide Range ◽

Core Components ◽

Temperature Entrainment ◽

Daily Time

Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster : the transcripts and proteins for the clock genes period ( per ) and timeless ( tim ). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per . The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2 . An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the ‘Tim 4’ genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting.

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