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The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock.

Heussen R, Whitmore D - Comput Math Methods Med (2015)

Bottom Line: Here we investigate how the circadian clock is entrained by external cues such as light.Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal.Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, UCL, Physics Building, Gower Place, London WC1E 6BT, UK.

ABSTRACT
The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

No MeSH data available.


Related in: MedlinePlus

Core components of the circadian clock in zebrafish.
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fig1: Core components of the circadian clock in zebrafish.

Mentions: Looking at biological oscillators in general, negative feedback is essential, which ensures a network is carried back to its starting point, while a sufficient delay ensures that reactions do not settle on a stable steady state. It has been found that oscillations are impossible in a two-component negative feedback loop but require at least three components [17], and accordingly molecular feedback loops based on various clock genes have been identified. There is now also affirmation of nontranscriptional, posttranslational mechanisms, such as protein phosphorylation. Identified zebrafish clock genes include Clock, Bmal, period, and cryptochrome genes [12]. It should also be noted that one of the characteristic features of the zebrafish clock is the presence of extra copies of the key clock genes. The core clock components (see Figure 1) constitute an autoregulatory feedback loop, with Clock and Bmal1 heterodimerizing and activating transcription of period (Per) [18] and cryptochrome (Cry) genes, which in turn inhibit Clock/Bmal1. In addition, it was shown that Cry1a is upregulated by light and may directly interact with specific regions of Clock (PAS B) and Bmal1 (bHLH, PAS B, and C-terminal domains), blocking their ability to form an active dimer and initiate downstream transcriptional activation [19]. There is also a stabilizing feedback loop, where Rev-Erb α and Rora are believed to direct rhythmic expression of the Clock and Bmal genes.


The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock.

Heussen R, Whitmore D - Comput Math Methods Med (2015)

Core components of the circadian clock in zebrafish.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663325&req=5

fig1: Core components of the circadian clock in zebrafish.
Mentions: Looking at biological oscillators in general, negative feedback is essential, which ensures a network is carried back to its starting point, while a sufficient delay ensures that reactions do not settle on a stable steady state. It has been found that oscillations are impossible in a two-component negative feedback loop but require at least three components [17], and accordingly molecular feedback loops based on various clock genes have been identified. There is now also affirmation of nontranscriptional, posttranslational mechanisms, such as protein phosphorylation. Identified zebrafish clock genes include Clock, Bmal, period, and cryptochrome genes [12]. It should also be noted that one of the characteristic features of the zebrafish clock is the presence of extra copies of the key clock genes. The core clock components (see Figure 1) constitute an autoregulatory feedback loop, with Clock and Bmal1 heterodimerizing and activating transcription of period (Per) [18] and cryptochrome (Cry) genes, which in turn inhibit Clock/Bmal1. In addition, it was shown that Cry1a is upregulated by light and may directly interact with specific regions of Clock (PAS B) and Bmal1 (bHLH, PAS B, and C-terminal domains), blocking their ability to form an active dimer and initiate downstream transcriptional activation [19]. There is also a stabilizing feedback loop, where Rev-Erb α and Rora are believed to direct rhythmic expression of the Clock and Bmal genes.

Bottom Line: Here we investigate how the circadian clock is entrained by external cues such as light.Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal.Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, UCL, Physics Building, Gower Place, London WC1E 6BT, UK.

ABSTRACT
The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

No MeSH data available.


Related in: MedlinePlus