It's time to swim! Zebrafish and the circadian clock (original) (raw)
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Starting the Zebrafish Pineal Circadian Clock with a Single Photic Transition
Endocrinology, 2006
The issue of what starts the circadian clock ticking was addressed by studying the developmental appearance of the daily rhythm in the expression of two genes in the zebrafish pineal gland that are part of the circadian clock system. One encodes the photopigment exorhodopsin and the other the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT2). Significant daily rhythms in AANAT2 mRNA abundance were detectable for several days after fertilization in animals maintained in a normal or reversed lighting cycle providing 12 h of light and 12 h of dark. In contrast, these rhythms do not develop if animals are maintained in
Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior
PLOS Genetics, 2016
The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.
Journal of Neuroendocrinology, 2005
In zebrafish, the pineal gland is a photoreceptive organ that contains an intrinsic circadian oscillator and exhibits rhythmic arylalkylamine-N-acetyltransferase (zfaanat2) mRNA expression. In the present study, we investigated the role of light and of a clock gene, zperiod2 (zper2), in the development of this rhythm. Analysis of zfaanat2 mRNA expression in the pineal gland of 3-day-old zebrafish embryos after exposure to different photoperiodic regimes indicated that light is required for proper development of the circadian clock-controlled rhythmic expression of zfaanat2, and that a 1-h light pulse is sufficient to initiate this rhythm. Analysis of zper2 mRNA expression in zebrafish embryos exposed to different photoperiodic regimes indicated that zper2 expression is transiently up-regulated by light but is not regulated by the circadian oscillator. To establish the association between light-induced zper2 expression and light-induced clock-controlled zfaanat2 rhythm, zPer2 knock-down experiments were performed. The zfaanat2 mRNA rhythm, induced by a 1-h light pulse, was abolished in zPer2 knock-down embryos. These experiments indicated that light-induced zper2 expression is crucial for establishment of the clock-controlled zfaanat2 rhythm in the zebrafish pineal gland.
Zebrafish circadian clocks: cells that see light
In the classical view of circadian clock organization, the daily rhythms of most organisms were thought to be regulated by a central, 'master' pacemaker, usually located within neural structures of the animal. However, with the results of experiments performed in zebrafish, mammalian cell lines and, more recently, mammalian tissues, this view has changed to one where clock organization is now seen as being highly decentralized. It is clear that clocks exist in the peripheral tissues of animals as diverse as Drosophila, zebrafish and mammals. In the case of Drosophila and zebrafish, these tissues are also directly lightresponsive. This light sensitivity and direct clock entrainability is also true for zebrafish cell lines and earlystage embryos. Using luminescent reporter cell lines containing clock gene promoters driving the expression of luciferase and single-cell imaging techniques, we have been able to show how each cell responds rapidly to a single light pulse by being shifted to a common phase, equivalent to the early day. This direct light sensitivity might be related to the requirement for light in these cells to activate the transcription of genes involved in DNA repair. It is also clear that the circadian clock in zebrafish regulates the timing of the cell cycle, demonstrating the wide impact that this light sensitivity and daily rhythmicity has on the biology of zebrafish.
Circadian Photoreception in the Zebrafish (Danio rerio) Pineal Gland
2006
The zebrafish pineal gland is a photoreceptive organ that contains an intrinsic circadian oscillator which drives daily rhythms of gene expression and the melatonin hormonal signal. Circadian rhythms of melatonin in the blood, peaking at night are design to modulate circadian and annual rhythms in all vertebrates. The source of rhythmic melatonin secretion is daily changes in the activity of Arylalkylamin Nacetyl transferase (AANAT). Zebrafish AANAT (zfAANAT2) activity is regulated by light and by the circadian oscillator in the pineal gland. Light pulse during the night triggers an acute degradation of AANAT protein in the pineal photoreceptor cell. In addition, daily-rhythmic transcription of zfaanat2 is regulated by the circadian oscillator. In zebrafish embryos, zfAanat2 mRNA expression begins at 22 h postfertilization (hpf), soon after the pineal is formed and clock-controlled rhythm of its transcript begins on the second day of development. In the studies presented here, I hav...
Zebrafish Clock rhythmic expression reveals independent peripheral circadian oscillators
Nature neuroscience, 1998
The only vertebrate clock gene identified by mutagenesis is mouse Clock, which encodes a bHLH-PAS transcription factor. We have cloned Clock in zebrafish and show that, in contrast to its mouse homologue, it is expressed with a pronounced circadian rhythm in the brain and in two defined pacemaker structures, the eye and the pineal gland. Clock oscillation was also found in other tissues, including kidney and heart. In these tissues, expression of Clock continues to oscillate in vitro. This demonstrates that self-sustaining circadian oscillators exist in several vertebrate organs, as was previously reported for invertebrates.
Autonomous onset of the circadian clock in the zebrafish embryo
The EMBO Journal, 2008
On the first day of development a circadian clock becomes functional in the zebrafish embryo. How this oscillator is set in motion remains unclear. We demonstrate that zygotic period1 transcription begins independent of light exposure. Pooled embryos maintained in darkness and under constant temperature show elevated non-oscillating levels of period1 expression. Consequently, there is no maternal effect or developmental event that sets the phase of the circadian clock. Analysis of period1 transcription, at the cellular level in the absence of environmental stimuli, reveals oscillations in cells that are asynchronous within the embryo. Demonstrating an autonomous onset to rhythmic period1 expression. Transcription of clock1 and bmal1 is rhythmic in the adult, but constant during development in light-entrained embryos. Transient expression of dominant-negative DCLOCK blocks period1 transcription, thus showing that endogenous CLOCK is essential for the transcriptional regulation of period1 in the embryo. We demonstrate a default mechanism in the embryo that initiates the autonomous onset of the circadian clock. This embryonic clock is differentially regulated from that in the adult, the transition coinciding with the appearance of several clock output processes.
Developmental stage-specific regulation of the circadian clock by temperature in zebrafish
BioMed research international, 2014
The circadian clock enables animals to adapt their physiology and behaviour in anticipation of the day-night cycle. Light and temperature represent two key environmental timing cues (zeitgebers) able to reset this mechanism and so maintain its synchronization with the environmental cycle. One key challenge is to unravel how the regulation of the clock by zeitgebers matures during early development. The zebrafish is an ideal model for studying circadian clock ontogeny since the process of development occurs ex utero in an optically transparent chorion and many tools are available for genetic analysis. However, the role played by temperature in regulating the clock during zebrafish development is poorly understood. Here, we have established a clock-regulated luciferase reporter transgenic zebrafish line (Tg (-3.1) per1b::luc) to study the effects of temperature on clock entrainment. We reveal that under complete darkness, from an early developmental stage onwards (48 to 72 hpf), expos...
Analysis of a Gene Regulatory Cascade Mediating Circadian Rhythm in Zebrafish
PLoS Computational Biology, 2013
In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow lightinduced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms.