A spatial model of the plant circadian clock reveals design principles for coordinated timing

Individual plant cells possess a genetic network, the circadian clock, that times internal processes to the day‐night cycle. Mathematical models of the clock are typically either “whole‐plant” that ignore tissue or cell type‐specific clock behavior, or “phase‐only” that do not include molecular components. To address the complex spatial coordination observed in experiments, here we implemented a clock network model on a template of a seedling. In our model, the sensitivity to light varies across the plant, and cells communicate their timing via local or long‐distance sharing of clock components, causing their rhythms to couple. We found that both varied light sensitivity and long‐distance coupling could generate period differences between organs, while local coupling was required to generate the spatial waves of clock gene expression observed experimentally. We then examined our model under noisy light‐dark cycles and found that local coupling minimized timing errors caused by the noise while allowing each plant region to maintain a different clock phase. Thus, local sensitivity to environmental inputs combined with local coupling enables flexible yet robust circadian timing.     

A suite of photoreceptors entrains the plant circadian clock

Circadian rhythms in plants are relatively robust, as they are maintained both in constant light of high fluence rates and in darkness. Plant circadian clocks exhibit the expected modes of photoentrainment, including period modulation by ambient light and phase resetting by brief light pulses. Several of the phytochrome and cryptochrome photoreceptors responsible have been studied in detail. This review concentrates on the resulting patterns of entrainment and on the multiple proposed mechanisms of light input to the circadian oscillator components.     

GABA synchronizes clock cells within the suprachiasmatic circadian clock

The master clock in the suprachiasmatic nuclei (SCN) is composed of multiple, single-cell circadian clocks. We test the postulate that these individual "clock cells" can be synchronized to each other by the inhibitory transmitter gamma-aminobutyric acid (GABA). For these experiments, we monitored the firing rate rhythm of individual clock cells on fixed multielectrode plates in culture and tested the effects of GABA. The results show that the daily variation in responsiveness of the SCN to phase-shifting agents is manifested at the level of individual neurons. Moreover, GABA, acting through A-type receptors, can both phase shift and synchronize clock cells. We propose that GABA is an important synchronizer of SCN neurons in vivo.     

Precision of the Gonyaulax circadian clock

Under constant conditions, the circadian bioluminescent glow rhythm in populations (10(5) cells) of Gonyaulax polyedra is accurate to within 2 min/day. On successive days following the transfer to constant conditions, however, the glow exhibits a progressively broader waveform, implying that individual clocks in the population are drifting out of synchrony. Analysis of the glow waveform suggests that the standard deviation in circadian period among individual clocks is about 18 min and that the period of a given clock varies by less than this from one day to the next.     

Insect circadian clock outputs

Insects display an impressive variety of daily rhythms, which are most evident in their behaviour. Circadian timekeeping systems that generate these daily rhythms of physiology and behaviour all involve three interacting elements: the timekeeper itself (i.e. the clock), inputs to the clock through which it entrains and otherwise responds to environmental cues such as light and temperature, and outputs from the clock through which it imposes daily rhythms on various physiological and behavioural parameters. In insects, as in other animals, cellular clocks are embodied in clock neurons capable of sustained autonomous circadian rhythmicity, and those clock neurons are organized into clock circuits. Drosophila flies spend their entire lives in small areas near the ground, and use their circadian brain clock to regulate daily rhythms of rest and activity, so as to organize their behaviour appropriately to the daily rhythms of their local environment. Migratory locusts and butterflies, on the other hand, spend substantial portions of their lives high up in the air migrating long distances (sometimes thousands of miles) and use their circadian brain clocks to provide time-compensation to their sun-compass navigational systems. Interestingly, however, there appear to be substantial similarities in the cellular and network mechanisms that underlie circadian outputs in all insects.     

Impaired light detection of the circadian clock in a zebrafish melanoma model

The circadian clock controls the timing of the cell cycle in healthy tissues and clock disruption is known to increase tumourigenesis. Melanoma is one of the most rapidly increasing forms of cancer and the precise molecular circadian changes that occur in a melanoma tumor are unknown. Using a melanoma zebrafish model, we have explored the molecular changes that occur to the circadian clock within tumors. We have found disruptions in melanoma clock gene expression due to a major impairment to the light input pathway, with a parallel loss of light-dependent activation of DNA repair genes. Furthermore, the timing of mitosis in tumors is perturbed, as well as the regulation of certain key cell cycle regulators, such that cells divide arhythmically. The inability to co-ordinate DNA damage repair and cell division is likely to promote further tumourigenesis and accelerate melanoma development.     

The mammalian circadian clock

Organisms populating the earth are under the steady influence of daily and seasonal changes resulting from the planet's rotation and orbit around the sun. This periodic pattern most prominently manifested by the light-dark cycle has led to the establishment of endogenous circadian timing systems that synchronize biological functions to the environment. The mammalian circadian system is composed of many individual, tissue-specific clocks. To generate coherent physiological and behavioral responses, the phases of this multitude of clocks are orchestrated by the master circadian pacemaker residing in the suprachiasmatic nuclei of the brain. Genetic, biochemical and genomic approaches have led to major advances in understanding the molecular and cellular basis of mammalian circadian clock components and mechanisms.     

Silencing the circadian clock gene Clock using RNAi reveals dissociation of the circatidal clock from the circadian clock in the mangrove cricket

Whether a clock that generates a circatidal rhythm shares the same elements as the circadian clock is not fully understood. The mangrove cricket, Apteronemobius asahinai, shows simultaneously two endogenous rhythms in its locomotor activity; the circatidal rhythm generates active and inactive phases, and the circadian rhythm modifies activity levels by suppressing the activity during subjective day. In the present study, we silenced Clock (Clk), a master gene of the circadian clock, in A. asahinai using RNAi to investigate the link between the circatidal and circadian clocks. The abundance of Clk mRNA in the crickets injected with double-stranded RNA of Clk (dsClk) was reduced to a half of that in control crickets. dsClk injection also reduced mRNA abundance of another circadian clock gene period (per) and weakened diel oscillation in per mRNA expression. Examination of the locomotor rhythms under constant conditions revealed that the circadian modification was disrupted after silencing Clk expression, but the circatidal rhythm remained unaffected. There were no significant changes in the free-running period of the circatidal rhythm between the controls and the crickets injected with dsClk. Our results reveal that Clk is essential for the circadian clock, but is not required for the circatidal clock. From these results we propose that the circatidal rhythm of A. asahinai is driven by a clock, the molecular components of which are distinct from that of the circadian clock.     

Winding up the cyanobacterial circadian clock

The endogenous circadian clock of the cyanobacterium Synechococcus elongatus controls many cellular processes and confers an adaptive advantage on this organism in a competitive environment. To be advantageous, this internal biological oscillator must be reset daily to remain in synchrony with its environment and to transduce temporal information to control behaviors at appropriate times of day. Recent studies have discovered new components of these input and output pathways of the clock that help to 'wind up' our understanding of the clock system as a whole. Here we review the mechanisms by which S. elongatus maintains internal time, discuss how external stimuli affect this oscillation, and evaluate the mechanisms underlying circadian controlled cellular events.     

Precision of theGonyaulax circadian clock

Under constant conditions, the circadian bioluminescent glow rhythm in populations (10⁵ cells) ofGonyaulax polyedra is accurate to within 2 min/day. On successive days following the transfer to constant conditions, however, the glow exhibits a progressively broader waveform, implying that individual clocks in the population are drifting out of synchrony. Analysis of the glow waveform suggests that the standard deviation in circadian period among individual clocks is about 18 min and that the period of a given clock varies by less than this from one day to the next.     

Signalling entrains the peripheral circadian clock

In mammals, 24-h rhythms of behaviour and physiology are regulated by the circadian clock. The circadian clock is controlled by a central clock in the brain's suprachiasmatic nucleus (SCN) that synchronizes peripheral clocks in peripheral tissues. Clock genes in the SCN are primarily entrained by light. Increasing evidence has shown that peripheral clocks are also regulated by light and hormones independent of the SCN. How the peripheral clocks deal with internal signals is dependent on the relevance of a specific cue to a specific tissue. In different tissues, most genes that are under circadian control are not overlapping, revealing the tissue-specific control of peripheral clocks. We will discuss how different signals control the peripheral clocks in different peripheral tissues, such as the liver, gastrointestinal tract, and pancreas, and discuss the organ-to-organ communication between the peripheral clocks at the molecular level.     

生物钟的基因调控

从细菌到哺乳动物的大多数生物都存在分子时钟,也就是生物钟。它的存在使生物的生理,生化,行为表现出以24小时为周期的节律性。本文从基因组成以及节律发生的分子机制等方面,对昼夜节街生物钟进行综述。