Gene Symbol: clocka
Description: clock circadian regulator a
Alias: clock, zCLOCK1, zfCLOCK1, circadian locomoter output cycles protein kaput, Clock1a, circadian locomotor output cycles kaput a, clk1
Species: zebrafish

Top Publications

  1. Tamai T, Young L, Whitmore D. Light signaling to the zebrafish circadian clock by Cryptochrome 1a. Proc Natl Acad Sci U S A. 2007;104:14712-7 pubmed
    Zebrafish tissues and cells have the unusual feature of not only containing a circadian clock, but also being directly light-responsive...
  2. Dekens M, Whitmore D. Autonomous onset of the circadian clock in the zebrafish embryo. EMBO J. 2008;27:2757-65 pubmed publisher
    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...
  3. Hirayama J, Fukuda I, Ishikawa T, Kobayashi Y, Todo T. New role of zCRY and zPER2 as regulators of sub-cellular distributions of zCLOCK and zBMAL proteins. Nucleic Acids Res. 2003;31:935-43 pubmed
    ..Six CRYs exist in zebrafish, of which zCRY1a strongly represses zCLOCK1: zBMAL3-mediated transcription, but zCRY3 does not...
  4. Appelbaum L, Anzulovich A, Baler R, Gothilf Y. Homeobox-clock protein interaction in zebrafish. A shared mechanism for pineal-specific and circadian gene expression. J Biol Chem. 2005;280:11544-51 pubmed
    ..of the PRDM mediate a synergistic effect of the photoreceptor-specific homeobox OTX5 and rhythmically expressed clock protein heterodimer, BMAL/CLOCK, on zfaanat2 expression...
  5. Lahiri K, Vallone D, Gondi S, Santoriello C, Dickmeis T, Foulkes N. Temperature regulates transcription in the zebrafish circadian clock. PLoS Biol. 2005;3:e351 pubmed
    It has been well-documented that temperature influences key aspects of the circadian clock. Temperature cycles entrain the clock, while the period length of the circadian cycle is adjusted so that it remains relatively constant over a ..
  6. Vatine G, Vallone D, Appelbaum L, Mracek P, Ben Moshe Z, Lahiri K, et al. Light directs zebrafish period2 expression via conserved D and E boxes. PLoS Biol. 2009;7:e1000223 pubmed publisher
    For most species, light represents the principal environmental signal for entraining the endogenous circadian clock. The zebrafish is a fascinating vertebrate model for studying this process since unlike mammals, direct exposure of most ..
  7. Idda M, Kage E, López Olmeda J, Mracek P, Foulkes N, Vallone D. Circadian timing of injury-induced cell proliferation in zebrafish. PLoS ONE. 2012;7:e34203 pubmed publisher
    ..using the regenerating adult zebrafish caudal fin as a model, we have demonstrated an involvement of the circadian clock in timing cell proliferation following injury...
  8. Whitmore D, Foulkes N, Sassone Corsi P. Light acts directly on organs and cells in culture to set the vertebrate circadian clock. Nature. 2000;404:87-91 pubmed
    The expression of clock genes in vertebrates is widespread and not restricted to classical clock structures...
  9. Pando M, Pinchak A, Cermakian N, Sassone Corsi P. A cell-based system that recapitulates the dynamic light-dependent regulation of the vertebrate clock. Proc Natl Acad Sci U S A. 2001;98:10178-83 pubmed
    ..Using this system, we show distinct and differential light-dependent gene activation for several central clock components. In particular, activation of Per2 expression is shown to be strictly regulated and dependent on light...

More Information


  1. Li Y, Li G, Wang H, Du J, Yan J. Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish. PLoS Comput Biol. 2013;9:e1002940 pubmed publisher
    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...
  2. Li P, Chaurasia S, Gao Y, Carr A, Iuvone P, Li L. CLOCK is required for maintaining the circadian rhythms of Opsin mRNA expression in photoreceptor cells. J Biol Chem. 2008;283:31673-8 pubmed publisher
    ..Functional expression of Clock, a circadian clock gene that contributes to the central circadian pacemaker, was found to play an important role ..
  3. Dekens M, Santoriello C, Vallone D, Grassi G, Whitmore D, Foulkes N. Light regulates the cell cycle in zebrafish. Curr Biol. 2003;13:2051-7 pubmed
    ..persist for several days after transfer to DD, both observations pointing to the involvement of the circadian clock. We show that the number of LD cycles experienced is essential for establishing this rhythm during larval ..
  4. Dickmeis T, Lahiri K, Nica G, Vallone D, Santoriello C, Neumann C, et al. Glucocorticoids play a key role in circadian cell cycle rhythms. PLoS Biol. 2007;5:e78 pubmed
    b>Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems...
  5. Xiao B, Chen T, Zhong Y. Possible molecular mechanism underlying cadmium-induced circadian rhythms disruption in zebrafish. Biochem Biophys Res Commun. 2016;481:201-205 pubmed publisher
    ..The mRNA levels of clock1a, bmal1b, per2 and per1b in two groups were determined. Microarray data were generated in two group of samples...
  6. Cermakian N, Whitmore D, Foulkes N, Sassone Corsi P. Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function. Proc Natl Acad Sci U S A. 2000;97:4339-44 pubmed
    Most clock genes encode transcription factors that interact to elicit cooperative control of clock function...
  7. Di Rosa V, Frigato E, López Olmeda J, Sánchez Vázquez F, Bertolucci C. The Light Wavelength Affects the Ontogeny of Clock Gene Expression and Activity Rhythms in Zebrafish Larvae. PLoS ONE. 2015;10:e0132235 pubmed publisher
    ..However, to date, little is known about the impact of light wavelengths during the ontogeny of the molecular clock and the behavioural rhythmicity...
  8. Stankiewicz A, McGowan E, Yu L, Zhdanova I. Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging. Int J Mol Sci. 2017;18: pubmed publisher
    ..An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can ..
  9. Ye Q, Chen D, Xi Y, Li J, Shao J, Li L. Effects of light illumination and the expression of wee1 on tissue regeneration in adult zebrafish. Biochem Biophys Res Commun. 2012;428:132-6 pubmed publisher
    ..Alterations in lighting conditions or inhibition of wee1 expression result in decreases in fin regeneration after injury. ..
  10. Khan Z, Yumnamcha T, Rajiv C, Sanjita Devi H, Mondal G, Devi S, et al. Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): Differential expression and a possible interplay. Gen Comp Endocrinol. 2016;233:16-31 pubmed publisher
    ..of melatonin biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to whole brain in normal (LD=12h L:12h D) and altered ..
  11. Ren D, Ji C, Wang X, Wang H, Hu B. Endogenous melatonin promotes rhythmic recruitment of neutrophils toward an injury in zebrafish. Sci Rep. 2017;7:4696 pubmed publisher
    ..disrupted migrating rhythmicity of neutrophils in aanat2 -/- zebrafish is independent of the circadian clock. Further, we also found that endogenous melatonin enhances neutrophils migration likely by inducing the expression ..
  12. Hirayama J, Nakamura H, Ishikawa T, Kobayashi Y, Todo T. Functional and structural analyses of cryptochrome. Vertebrate CRY regions responsible for interaction with the CLOCK:BMAL1 heterodimer and its nuclear localization. J Biol Chem. 2003;278:35620-8 pubmed
    ..mCRY1 and zCRY1a repress CLOCK:BMAL1-mediated transcription, whereas zCRY3 does not...
  13. Purushothaman S, Saxena S, Meghah V, Meena Lakshmi M, Singh S, Brahmendra Swamy C, et al. Proteomic and gene expression analysis of zebrafish brain undergoing continuous light/dark stress. J Sleep Res. 2015;24:458-65 pubmed publisher
    ..It is hypothesized that the differential regulation of these genes might lead to the discovery of potential diagnostic markers for gaining insight into the light/dark-associated stress in humans. ..
  14. Kopp R, Schwerte T, Egg M, Sandbichler A, Egger B, Pelster B. Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required. Physiol Genomics. 2010;42A:8-23 pubmed publisher
    ..The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae. ..
  15. Zhong H, Zou H, Semenov M, Moshinsky D, He X, Huang H, et al. Characterization and development of novel small-molecules inhibiting GSK3 and activating Wnt signaling. Mol Biosyst. 2009;5:1356-60 pubmed publisher
    ..Together, 3F8 and its derivatives could be useful as new reagents and potential therapeutic candidates for GSK3 related diseases. ..
  16. Ishikawa T, Hirayama J, Kobayashi Y, Todo T. Zebrafish CRY represses transcription mediated by CLOCK-BMAL heterodimer without inhibiting its binding to DNA. Genes Cells. 2002;7:1073-86 pubmed
    b>CLOCK and BMAL1 proteins, members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors which bind to the E-box DNA motif, are required for the high-level expression of the circadian clock genes period (..
  17. Li Y, Li G, Görling B, Luy B, Du J, Yan J. Integrative analysis of circadian transcriptome and metabolic network reveals the role of de novo purine synthesis in circadian control of cell cycle. PLoS Comput Biol. 2015;11:e1004086 pubmed publisher
    Metabolism is the major output of the circadian clock in many organisms. We developed a computational method to integrate both circadian gene expression and metabolic network...
  18. Triqueneaux G, Thenot S, Kakizawa T, Antoch M, Safi R, Takahashi J, et al. The orphan receptor Rev-erbalpha gene is a target of the circadian clock pacemaker. J Mol Endocrinol. 2004;33:585-608 pubmed
    ..P2 (Rev-erbalpha2) contain several E-box DNA sequences which function as response elements for the core circadian-clock components: CLOCK and BMAL1...
  19. Hirayama J, Miyamura N, Uchida Y, Asaoka Y, Honda R, Sawanobori K, et al. Common light signaling pathways controlling DNA repair and circadian clock entrainment in zebrafish. Cell Cycle. 2009;8:2794-801 pubmed
    ..The zebrafish circadian clock is controlled by a cell-autonomous and light-dependent oscillator, where zCRY1a functions as an important mediator ..
  20. Huang J, Zhong Z, Wang M, Chen X, Tan Y, Zhang S, et al. Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior. J Neurosci. 2015;35:2572-87 pubmed publisher
    ..We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes ..
  21. Zhao Y, Zhang K, Fent K. Regulation of zebrafish (Danio rerio) locomotor behavior and circadian rhythm network by environmental steroid hormones. Environ Pollut. 2018;232:422-429 pubmed publisher
    ..different natural and synthetic steroid hormones on the locomotor behavior and the transcriptional levels of core clock genes in zebrafish eleuthero-embryos (Danio rerio)...
  22. Kopp R, Billecke N, Legradi J, den Broeder M, Parekh S, Legler J. Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?. Int J Obes (Lond). 2016;40:824-32 pubmed publisher
    ..b>Clock and adipogenic gene expression was quantitative real time PCR...
  23. Egg M, Köblitz L, Hirayama J, Schwerte T, Folterbauer C, Kurz A, et al. Linking oxygen to time: the bidirectional interaction between the hypoxic signaling pathway and the circadian clock. Chronobiol Int. 2013;30:510-29 pubmed publisher
    The circadian clock and the hypoxic signaling pathway play critical roles in physiological homeostasis as well as in tumorgenesis...
  24. Liu C, Hu J, Qu C, Wang L, Huang G, Niu P, et al. Molecular evolution and functional divergence of zebrafish (Danio rerio) cryptochrome genes. Sci Rep. 2015;5:8113 pubmed publisher
    ..These findings provide a better understanding of evolution of zebrafish cry genes. ..
  25. Cavallari N, Frigato E, Vallone D, Fröhlich N, López Olmeda J, Foá A, et al. A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception. PLoS Biol. 2011;9:e1001142 pubmed publisher
    The circadian clock is synchronized with the day-night cycle primarily by light...
  26. Tan Y, DeBruyne J, Cahill G, Wells D. Identification of a mutation in the Clock1 gene affecting zebrafish circadian rhythms. J Neurogenet. 2008;22:149-66 pubmed publisher
    ..This isoleucine is tightly conserved in the Clock genes of several different species, and the I254N was not seen in any of the wild-type zebrafish population tested...
  27. Egg M, Tischler A, Schwerte T, Sandbichler A, Folterbauer C, Pelster B. Endurance exercise modifies the circadian clock in zebrafish (Danio rerio) temperature independently. Acta Physiol (Oxf). 2012;205:167-76 pubmed publisher
    Several rodent and human studies revealed that physical exercise acts as a non-photic zeitgeber for the circadian clock. The intrinsic entraining mechanism is still unknown, although it was assumed that the exercise-mediated increase in ..
  28. Amaral I, Johnston I. Circadian expression of clock and putative clock-controlled genes in skeletal muscle of the zebrafish. Am J Physiol Regul Integr Comp Physiol. 2012;302:R193-206 pubmed publisher
    ..Expression of the two paralogs of cry2 occurred in phase with clock1a/1b...
  29. Toloza Villalobos J, Arroyo J, Opazo J. The circadian clock of teleost fish: a comparative analysis reveals distinct fates for duplicated genes. J Mol Evol. 2015;80:57-64 pubmed publisher
    The circadian clock is a central oscillator that coordinates endogenous rhythms. Members of six gene families underlie the metabolic machinery of this system...
  30. Rhee J, Kim B, Lee B, Hwang U, Lee Y, Lee J. Cloning of circadian rhythmic pathway genes and perturbation of oscillation patterns in endocrine disrupting chemicals (EDCs)-exposed mangrove killifish Kryptolebias marmoratus. Comp Biochem Physiol C Toxicol Pharmacol. 2014;164:11-20 pubmed publisher
    To investigate the effect of endocrine disrupting chemicals (EDCs) on the circadian rhythm pathway, we cloned clock and circadian rhythmic pathway-associated genes (e.g...
  31. Bian S, Zheng X, Sun H, Chen J, Lu Y, Liu Y, et al. Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signaling in the zebrafish embryo. J Biol Chem. 2017;292:14165-14175 pubmed publisher
    ..Here we show that Clock1a coordinated mesoderm development and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal-..
  32. Jensen L, Cao Z, Nakamura M, Yang Y, Bräutigam L, Andersson P, et al. Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish. Cell Rep. 2012;2:231-41 pubmed publisher
    ..Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired ..
  33. Xiao B, Cui L, Ding C, Wang H. Effects of Lithium and 2,4-Dichlorophenol on Zebrafish: Circadian Rhythm Disorder and Molecular Effects. Zebrafish. 2017;14:209-215 pubmed publisher
    ..The mRNA levels of circadian clock-related genes, including clock1a, bmal1b, per2, and per1b, were determined...
  34. Abe T, Ishikawa T, Masuda T, Mizusawa K, Tsukamoto T, Mitani H, et al. Molecular analysis of Dec1 and Dec2 in the peripheral circadian clock of zebrafish photosensitive cells. Biochem Biophys Res Commun. 2006;351:1072-7 pubmed
    ..zDEC1 and zDEC2 inhibited zCLOCK1:zBMAL3 mediated transcription as CRY1a. zDec1 and zDec2 mRNA showed robust circadian oscillation in BRF41 cells...
  35. Cruz B, Brongar L, Popiolek P, Gonçalvez B, Figueiredo M, Amaral I, et al. Clock genes expression and locomotor activity are altered along the light-dark cycle in transgenic zebrafish overexpressing growth hormone. Transgenic Res. 2017;26:739-752 pubmed publisher
    ..Gene expression of clock paralogs was reduced in GH fish at the beginning of the dark phase, leading to diminished expression amplitude ..
  36. Egg M, Paulitsch M, Ennemoser Y, Wüstenhagen A, Schwerte T, Sandbichler A, et al. Chronodisruption increases cardiovascular risk in zebrafish via reduced clearance of senescent erythrocytes. Chronobiol Int. 2014;31:680-9 pubmed publisher
    The circadian clock and the hypoxic signaling pathway play critical roles in physiological homeostasis as well as in pathogenesis...