Coupling Controls the Synchrony of Clock Cells in Development and Knockouts

Tokuda, Isao T.; Ono, Daisuke; Ananthasubramaniam, Bharath; Honma, Sato; Honma, Ken‐ichi; Herzel, Hanspeter

doi:10.1016/j.bpj.2015.09.024

Cited by 22 publications

(25 citation statements)

References 44 publications

(68 reference statements)

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“…Previously, we found that medium exchange induced phase-dependent phase-shifts of circadian Bmal1 rhythm in the cultured SCN slice of neonatal mice but not of the adult 19 . Thus, the circadian rhythms in the SCN make developmentally different responses to environmental perturbations, which could be ascribed to the SCN neural network 20 , 21 and responsible for maternal entrainment in the early life and light entrainment afterwards.…”

Section: Introductionmentioning

confidence: 99%

Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

Nishide

Honma

2018

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Circadian rhythms in clock genes, Bmal1 and Per2 expression were monitored simultaneously in the cultured slice of mouse suprachiasmatic nucleus (SCN) by dual bioluminescent reporters. In the neonatal SCN, the phase-relation between the Bmal1 and Per2 rhythms were significantly changed during culture. Medium exchange produced phase-dependent phase shifts (PRCm) in the Bmal1 rhythms, but not in the Per2 rhythms. As a result, the two circadian rhythms were temporally dissociated after medium exchange. In the adult SCN, the phase-relation between the two rhythms was kept constant during culture at least up to 20 cycles. The amplitude of PRCm in the adult SCN was significantly attenuated in the Bmal1 rhythm, whereas a PRCm was developed in the Per2 rhythm. The circadian period was not systematically affected by medium exchange in either of rhythms, regardless of whether it was in the neonatal or the adult SCN. Tetrodotoxin, a sodium channel blocker, enhanced the phase-response in both rhythms but abolished the phase-dependency. In addition, tetrodotoxin lengthened the circadian period independent of the phase of administration. Thus, the Bmal1 and Per2 rhythms in the SCN are dissociable and likely regulated by distinct circadian oscillators. Bmal1 is the component of a Bmal1/REV-ERBa/ROR loop and Per2 a Per/Cry/BMAL1/CLOCK loop. Both loops could be molecular mechanisms of the two circadian oscillators that are coupled through the protein product of Bmal1. The coupling strength between the two oscillations depends on developmental stages.

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Section: Introductionmentioning

confidence: 99%

Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

Nishide

Honma

2018

Sci Rep

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“…Genetic oscillators are characterized by gene regulatory networks that autonomously generate time-periodic changes in gene product numbers of so-called cyclic genes [5,6,20]. This is typically achieved by a negative transcriptional feedback of the cyclic genes on themselves that involves a sufficiently large time delay [5,21,22]. In recent years, genetic oscillators have also been engineered in artificial The zebrafish somitogenesis oscillator as an example for coupled genetic oscillations.…”

Section: Introductionmentioning

confidence: 99%

Chemical event chain model of coupled genetic oscillators

2018

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We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

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“…While parameter dependencies of oscillator properties such as the amplitude or free-running period are usually intertwined in complex molecular models, the Poincaré oscillator (1, 2) conveniently treats these features as independent parameters. Thus, the impact of internal clock parameters on entrainment and synchronization properties can be studied in a straightforward manner as demonstrated in several studies (Abraham et al, 2010;Granada et al, 2013;Gu et al, 2014;Tokuda et al, 2015;Myung et al, 2018;Schmal et al, 2019). In the following we will represent the circadian clock of an organism by a Poincaré oscillator (1, 2) and study its entrainment under natural light environments, using a simple celestial mechanics derivation.…”

Section: The Poincaré Oscillator: a Conceptual Model For Limit Cycle mentioning

confidence: 99%

Clocks in the Wild: Entrainment to Natural Light

2020

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Entrainment denotes a process of coordinating the internal circadian clock to external rhythmic time-cues (Zeitgeber), mainly light. It is facilitated by stronger Zeitgeber signals and smaller period differences between the internal clock and the external Zeitgeber. The phase of entrainment ψ is a result of this process on the side of the circadian clock. On Earth, the period of the day-night cycle is fixed to 24 h, while the periods of circadian clocks distribute widely due to natural variation within and between species. The strength and duration of light depend locally on season and geographic latitude. Therefore, entrainment characteristics of a circadian clock vary under a local light environment and distribute along geoecological settings. Using conceptual models of circadian clocks, we investigate how local conditions of natural light shape global patterning of entrainment through seasons. This clock-side entrainment paradigm enables us to predict systematic changes in the global distribution of chronotypes.

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Coupling Controls the Synchrony of Clock Cells in Development and Knockouts

Cited by 22 publications

References 44 publications

Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

Chemical event chain model of coupled genetic oscillators

Clocks in the Wild: Entrainment to Natural Light

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