The circadian timekeeping system of Drosophila

Daily rhythms in behavior, physiology and metabolism are controlled by endogenous circadian clocks. At the heart of these clocks is a circadian oscillator that keeps circadian time, is entrained by environmental cues such as light and activates rhythmic outputs at the appropriate time of day. Genetic and molecular analyses in Drosophila have revealed important insights into the molecules and mechanisms underlying circadian oscillator function in all organisms. In this review I will describe the intracellular feedback loops that form the core of the Drosophila circadian oscillator and consider how they are entrained by environmental light cycles, where they operate within the fly and how they are thought to control overt rhythms in physiology and behavior. I will also discuss where work remains to be done to give a comprehensive picture of the circadian clock in Drosophila and likely many other organisms.     

Regulation of output from the plant circadian clock

Plants, like many other organisms, have endogenous biological clocks that enable them to organize their physiological, metabolic and developmental processes so that they occur at optimal times. The best studied of these biological clocks are the circadian systems that regulate daily (approximately 24 h) rhythms. At the core of the circadian system in every organism are oscillators responsible for generating circadian rhythms. These oscillators can be entrained (set) by cues from the environment, such as daily changes in light and temperature. Completing the circadian clock model are the output pathways that provide a link between the oscillator and the various biological processes whose rhythms it controls. Over the past few years there has been a tremendous increase in our understanding of the mechanisms of the oscillator and entrainment pathways in plants and many useful reviews on the subject. In this review we focus on the output pathways by which the oscillator regulates rhythmic plant processes. In the first part of the review we describe the role of the circadian system in regulation at all stages of a plant's development, from germination and growth to reproductive development as well as in multiple cellular processes. Indeed, the importance of a circadian clock for plants can be gauged by the fact that so many facets of plant development are under its control. In the second part of the review we describe what is known about the mechanisms by which the circadian system regulates these output processes.     

Focusing on the nuclear and subnuclear dynamics of light and circadian signalling

Circadian clocks provide organisms the ability to synchronize their internal physiological responses with the external environment. This process, termed entrainment, occurs through the perception of internal and external stimuli. As with other organisms, in plants, the perception of light is a critical for the entrainment and sustainment of circadian rhythms. Red, blue, far‐red, and UV‐B light are perceived by the oscillator through the activity of photoreceptors. Four classes of photoreceptors signal to the oscillator: phytochromes, cryptochromes, UVR8, and LOV‐KELCH domain proteins. In most cases, these photoreceptors localize to the nucleus in response to light and can associate to subnuclear structures to initiate downstream signalling. In this review, we will highlight the recent advances made in understanding the mechanisms facilitating the nuclear and subnuclear localization of photoreceptors and the role these subnuclear bodies have in photoreceptor signalling, including to the oscillator. We will also highlight recent progress that has been made in understanding the regulation of the nuclear and subnuclear localization of components of the plant circadian clock.     

The brown clock: circadian rhythms in stramenopiles

Circadian clocks allow organisms to anticipate environmental changes associated with the diurnal light/dark cycle. Circadian oscillators have been described in plants and green algae, cyanobacteria, animals and fungi, however, little is known about the circadian clocks of photosynthetic eukaryotes outside the green lineage. Stramenopiles are a diverse group of secondary endosymbionts whose plastid originated from a red alga. Photosynthetic stramenopiles, which include diatoms and brown algae, play key roles in biogeochemical cycles and are important components of marine ecosystems. Genome annotation efforts indicated the presence of a novel type of oscillator in these organisms and the first circadian clock component in a stramenopile has been recently discovered. This review summarizes the phenotypic characterization of circadian rhythms in stramenopiles and current efforts to determine the mechanisms of this ‘brown clock’. The elucidation of this brown clock will enable a deeper understanding of the role of self-sustained oscillations in the adaptation to life in marine environments.     

Constitutive expression of CIR1 (RVE2) affects several circadian-regulated processes and seed germination in Arabidopsis

Circadian clocks are endogenous auto-regulatory mechanisms that allow organisms, from bacteria to humans, to advantageously time a wide range of activities within 24 h environmental cycles. Here we report the identification and characterization of an MYB-related gene, designated Circadian 1 (CIR1), that is involved in circadian regulation in Arabidopsis. Expression of CIR1 is transiently induced by light and oscillates with a circadian rhythm. The rhythmic expression of CIR1 is controlled by the central oscillator. Constitutive expression of CIR1 resulted in a shorter period length for the rhythms of four central oscillator components, and much lower amplitude for the rhythms of central oscillator components CCA1 and LHY. Furthermore, CIR1 over-expression severely affected the circadian rhythms of its own RNA and those of the slave oscillator EPR1 and effector genes Lhcb and CAT3. Plants that constitutively expressed CIR1 displayed delayed flowering, longer hypocotyls and reduced seed germination in the dark. These results suggest that CIR1 is possibly part of a regulatory feedback loop that controls a subset of the circadian outputs and modulates the central oscillator.     

Comparative overviews of clock-associated genes of Arabidopsis thaliana and Oryza sativa

In higher plants, circadian rhythms are highly relevant to a wide range of biological processes. To such circadian rhythms, the clock (oscillator) is central, and recent intensive studies on the model higher plant Arabidopsis thaliana have begun to shed light on the molecular mechanisms underlying the functions of the central clock. Such representative clock-associated genes of A. thaliana are the homologous CCA1 and LHY genes, and five PRR genes that belong to a small family of pseudo-response regulators including TOC1. Others are GI, ZTL, ELF3, ELF4, LUX/PCL1, etc. In this context, a simple question arose as to whether or not the molecular picture of the model Arabidopsis clock is conserved in other higher plants. Here we made an effort to answer the question with special reference to Oryza sativa, providing experimental evidence that this model monocot also has a set of highly conserved clock-associated genes, such as those designated as OsCCA1, OsPRR-series including OsTOC1/OsPRR1, OsZTLs, OsPCL1 as well as OsGI. These results will provide us with insight into the general roles of plant circadian clocks, such as those for the photoperiodic control of flowering time that has a strong impact on the reproduction and yield in many higher plants.     

生物钟机制研究进展

由生物体内源性生物钟所产生的昼夜节律是近年来生命科学的研究热点之一。几种模型生物（蓝细菌、脉孢菌、拟南芥、果蝇、小鼠）的生物钟相关基因相继被克隆和鉴定,为理解昼夜节律的分子机制奠定了基础。振荡器蛋白对其编码基因的负反馈调控可能是不同生物的生物运作普遍机制,在此基础上,不同生物有不尽相同的调控方式;隐色素可能是高等生物的共同生物钟光受体。     

An Example of Circular Statistics in Chronobiological Studies: Analysis of Polymorphism in the Emergence Rhythms of Schistosoma Mansoni Cercariae

In the not too distant past, it was common belief that rhythms in the physical environment were the driving force, to which organisms responded passively, for the observed daily rhythms in measurable physiological and behavioral variables. The demonstration that this was not the case, but that both plants and animals possess accurate endogenous time-measuring machinery (i.e., circadian clocks) contributed to heightening interest in the study of circadian biological rhythms. In the last few decades, flourishing studies have demonstrated that most organisms have at least one internal circadian timekeeping device that oscillates with a period close to that of the astronomical day (i.e., 24h). To date, many of the physiological mechanisms underlying the control of circadian rhythmicity have been described, while the improvement of molecular biology techniques has permitted extraordinary advancements in our knowledge of the molecular components involved in the machinery underlying the functioning of circadian clocks in many different organisms, man included. In this review, we attempt to summarize our current understanding of the genetic and molecular biology of circadian clocks in cyanobacteria, fungi, insects, and mammals. (Chronobiology International, 17(4), 433–451, 2000)     

Circadian clocks: what makes them tick?

In the not too distant past, it was common belief that rhythms in the physical environment were the driving force, to which organisms responded passively, for the observed daily rhythms in measurable physiological and behavioral variables. The demonstration that this was not the case, but that both plants and animals possess accurate endogenous time-measuring machinery (i.e., circadian clocks) contributed to heightening interest in the study of circadian biological rhythms. In the last few decades, flourishing studies have demonstrated that most organisms have at least one internal circadian timekeeping device that oscillates with a period close to that of the astronomical day (i.e., 24h). To date, many of the physiological mechanisms underlying the control of circadian rhythmicity have been described, while the improvement of molecular biology techniques has permitted extraordinary advancements in our knowledge of the molecular components involved in the machinery underlying the functioning of circadian clocks in many different organisms, man included. In this review, we attempt to summarize our current understanding of the genetic and molecular biology of circadian clocks in cyanobacteria, fungi, insects, and mammals. (Chronobiology International, 17(4), 433-451, 2000)     

The current state and problems of circadian clock studies in cyanobacteria

Circadian rhythms have been observed in innumerable physiological processes in most of organisms. Recent molecular and genetic studies on circadian clocks in many organisms have identified and characterized several molecular regulatory factors that contribute to generation of such rhythms. The cyanobacterium is the simplest organism known to harbor circadian clocks, and it has become one of most successful model organisms for circadian biology. In this review, we will briefly summarize physiological observations and consideration of circadian rhythms in cyanobacteria, molecular genetics of the clock using Synechococcus, and current knowledge of the input and output pathways that support the cellular circadian system. Finally, we will document some current problems in the studies on the cyanobacterial circadian clock.     

Circadian timing mechanism in the prokaryotic clock system of cyanobacteria

Cyanobacteria are the simplest organisms known to exhibit circadian rhythms and have provided experimental model systems for the dissection of basic properties of circadian organization at the molecular, physiological, and ecological levels. This review focuses on the molecular and genetic mechanisms of circadian rhythm generation in cyanobacteria. Recent analyses have revealed the existence of multiple feedback processes in the prokaryotic circadian system and have led to a novel molecular oscillator model. Here, the authors summarize current understanding of, and open questions about, the cyanobacterial oscillator.     

Understanding circadian rhythmicity in Neurospora crassa: from behavior to genes and back again

Circadian clocks have been described in organisms ranging in complexity from unicells to mammals, in which they function to control daily rhythms in cellular activities and behavior. The significance of a detailed understanding of the clock can be appreciated by its ubiquity and its established involvement in human physiology, including endocrine function, sleep/wake cycles, psychiatric illness, and drug tolerances and effectiveness. Because the clock in all organisms is assembled within the cell and clock mechanisms are evolutionarily conserved, simple eukaryotes provide appropriate experimental systems for dissecting the clock. Significant progress has been made in deciphering the circadian system in Neurospora crassa using both genetic and molecular approaches, and Neurospora has contributed greatly to our understanding of (1) the feedback cycle that comprises a circadian oscillator, (2) the mechanisms by which the clock is kept in synchrony with the environment, and (3) the genes that reside in rhythmic output pathways. Importantly, the lessons learned in Neurospora are relevant to our understanding of clocks in higher eukaryotes.     

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.