Peripheral Circadian Oscillators in Mammals

Brown, Steven A.; Azzi, Abdelhalim

doi:10.1007/978-3-642-25950-0_3

Cited by 108 publications

(74 citation statements)

References 124 publications

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“…2). In turn, the cellular regulation of clock-controlled processes can be achieved by the same cis-acting elements that direct clock gene expression, by circadian cascades of downstream transcription factors or by systemic regulation via hormones, metabolic products and body temperature (Brown and Azzi, 2013). Recently, transcriptionindependent oscillation of protein oxidation has also been reported, but its mechanism remains as yet unknown (O'Neill and Reddy, 2011).…”

Section: An Overview Of the Mechanistic Basis Of Molecular Clocksmentioning

confidence: 99%

“…Supporting this widespread control, the circadian clock mechanism itself is cell-autonomous; most cells of the human body possess the same molecular clockwork. These clocks are then synchronized to one another via redundant systemic cues to ensure optimum correspondence with the environment (Brown and Azzi, 2013). For the most part, these cues originate from the suprachiasmatic nuclei (SCN) of the hypothalamus: the 'master clock' tissue in mammals.…”

Section: Introductionmentioning

confidence: 99%

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Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

Brown

2014

Development

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A biological 'circadian' clock conveys diurnal regulation upon nearly all aspects of behavior and physiology to optimize them within the framework of the solar day. From digestion to cardiac function and sleep, both cellular and systemic processes show circadian variations that coincide with diurnal need. However, recent research has shown that this same timekeeping mechanism might have been co-opted to optimize other aspects of development and physiology that have no obvious link to the 24 h day. For example, clocks have been suggested to underlie heterogeneity in stem cell populations, to optimize cycles of cell division during wound healing, and to alter immune progenitor differentiation and migration. Here, I review these circadian mechanisms and propose that they could serve as metronomes for a surprising variety of physiologically and medically important functions that far exceed the daily timekeeping roles for which they probably evolved.

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Section: An Overview Of the Mechanistic Basis Of Molecular Clocksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

Brown

2014

Development

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“…The SCN controls the rhythms of diverse physiological functions, including feeding, temperature cycles, and circulating hormones, which in turn synchronize the clocks of tissues throughout the body (2). Following lesions of the SCN, animal behavior becomes arrhythmic and internal synchrony among tissues throughout the body is lost (3)(4)(5).…”

mentioning

confidence: 99%

Local photic entrainment of the retinal circadian oscillator in the absence of rods, cones, and melanopsin

Buhr¹,

Gelder

2014

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

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Synchronization of the mammalian master circadian pacemaker to the daily light/dark cycle is mediated exclusively through retinal photoreceptors. The mammalian retina itself is also a self-sustained circadian oscillator. Here we report that the retinal molecular circadian clock can be entrained by lighting cycles in vitro, but that rods, cones, and melanopsin (Opn4) are not required for this entrainment. In vivo, retinas of Opn4;rd1/rd1 mice synchronize to light/dark cycles regardless of the phase of the master circadian pacemakers of the suprachiasmatic nuclei or the behavior of the animal. These data demonstrate that the retina uses a separate mechanism for local entrainment of its circadian clock than for entrainment of organism-level rhythmicity.circadian rhythm M ost mammalian tissues contain autonomous circadian clocks, and these oscillators are synchronized by the "master circadian pacemaker," which is localized in the suprachiasmatic nucleus (SCN) of the hypothalamus (1). The SCN controls the rhythms of diverse physiological functions, including feeding, temperature cycles, and circulating hormones, which in turn synchronize the clocks of tissues throughout the body (2). Following lesions of the SCN, animal behavior becomes arrhythmic and internal synchrony among tissues throughout the body is lost (3-5). Photic entrainment of the mammalian SCN (and thus the animal's behavior) is mediated exclusively through photoreception in the retina (6, 7). Although outer retinal (rod/cone)-based and melanopsinexpressing retinal ganglion cell-based photoreceptors are each sufficient for circadian entrainment of behavior, animals lacking rods, cones, and melanopsin (Opn4) cannot entrain to external light/dark cycles (8-10).The mammalian retina itself is also a self-sustained circadian oscillator (11), and many retinal physiologic functions oscillate with a 24-h period. These include transcription and translation of photoreceptor genes, neurotransmitter synthesis and release, interphotoreceptor coupling, disk shedding in rods, and amplitude of the electroretinogram (ERG) (12-18). More than 1,000 genes in the retina have a significant 24-h diurnal rhythm in transcript abundance (15). When the core circadian clock gene Bmal1 is deleted specifically in the retina (rendering it incapable of free-running rhythmicity), transcriptional and ERG rhythmicity are lost and ERG amplitudes are reduced at all times of day, suggesting that local circadian rhythmicity is required for normal retinal function (15). The circadian clock in the mammalian retina persists in culture, and can be measured ex vivo by neurotransmitter release or by luminescent reporters of circadianly expressed core clock genes (11,19). Importantly, the retinal rhythm of melatonin synthesis can be synchronized directly by light/dark cycles in culture (11,20), demonstrating that the SCN is not necessary for synchronization of retinal rhythms. Here we demonstrate that the retinal clock remains entrained to the light/dark cycle regardless of SCN and behavioral phase...

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“…Though the SCN clock is the circadian pacemaker for the whole organism, the peripheral circadian oscillators in mammals are not just a passive medium. It has been shown that peripheral clocks are cell-autonomous and can produce rhythm irrespective of SCN [36]. Thus, the master clock rather synchronizes peripheral clocks that work locally and autonomously than sends direct commands to control the local circadian physiology.…”

Section: General Principlesmentioning

confidence: 99%

Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

et al. 2015

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We propose a multiscale chemo-mechanical model of cancer tumor development in epithelial tissue. The model is based on the transformation of normal cells into a cancerous state triggered by a local failure of spatial synchronization of the circadian rhythm. The model includes mechanical interactions and a chemical signal exchange between neighboring cells, as well as a division of cells and intercalation that allows for modification of the respective parameters following transformation into the cancerous state. The numerical simulations reproduce different dephasing patterns-spiral waves and quasistationary clustering, with the latter being conducive to cancer formation. Modification of mechanical properties reproduces a distinct behavior of invasive and localized carcinoma.

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Peripheral Circadian Oscillators in Mammals

Cited by 108 publications

References 124 publications

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

Local photic entrainment of the retinal circadian oscillator in the absence of rods, cones, and melanopsin

Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

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