The Fish Circadian Timing System: The Illuminating Case of Light-Responsive Peripheral Clocks

  • Cristina Pagano
  • Rosa Maria Ceinos
  • Daniela Vallone
  • Nicholas S. Foulkes


This chapter is dedicated to the circadian timing system of fish. In particular, we focus on one unique aspect of fish clocks that is helping us to build a more general understanding of the mechanisms and evolution of the circadian timing system in vertebrates. While in mammals peripheral clocks rely on systemic signals for their entrainment, in fish these clocks are directly light entrainable. Furthermore, in fish the transcription of a set of genes, including key clock genes, is induced upon the direct exposure of cells and tissues to light. We show that studying light-inducible gene expression in fish has revealed how fundamental changes in signal transduction systems have occurred during the evolution of mammals and fish. Furthermore, we explain how blind cavefish can serve as powerful models to further advance our understanding of the complexity of fish photoreceptor systems.


Circadian Clock Clock Gene Clock Gene Expression Peripheral Clock Cave Environment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Schibler U, Gotic I, Saini C, Gos P, Curie T, Emmenegger Y, et al (2015) Clock-talk: interactions between central and peripheral circadian oscillators in mammals. Cold Spring Harbor symposia on quantitative biology, December 18, 2015:  10.1101/sqb.2015.80.027490
  2. 2.
    Sassone-Corsi P, Whitmore D, Foulkes NS (2000) Light acts directly on organs and cells in culture to set the vertebrate circadian clock. Nature 404:87–91CrossRefPubMedGoogle Scholar
  3. 3.
    Ito C, Goto SG, Shiga S, Tomioka K, Numata H (2008) Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster. Proc Natl Acad Sci 105:8446–8451CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Krishnan B, Dryer SE, Hardin PE (1999) Circadian rhythms in olfactory responses of Drosophila melanogaster. Nature 400:375–378CrossRefPubMedGoogle Scholar
  5. 5.
    Giebultowicz JM, Stanewsky R, Hall JC, Hege DM (2000) Transplanted Drosophila excretory tubules maintain circadian clock cycling out of phase with the host. Curr Biol 10:107–110CrossRefPubMedGoogle Scholar
  6. 6.
    Zylka MJ, Shearman LP, Weaver DR, Reppert SM (1998) Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron 20:1103–1110CrossRefPubMedGoogle Scholar
  7. 7.
    Shearman LP, Zylka MJ, Weaver DR, Kolakowski LF, Reppert SM (1997) Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron 19:1261–1269CrossRefPubMedGoogle Scholar
  8. 8.
    Whitmore D, Foulkes NS, Strähle U, Sassone-Corsi P (1998) Zebrafish clock rhythmic expression reveals independent peripheral circadian oscillators. Nat Neurosci 1:701–707CrossRefPubMedGoogle Scholar
  9. 9.
    Cermakian N, Whitmore D, Foulkes NS, Sassone-Corsi P (2000) Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function. Proc Natl Acad Sci U S A 97:4339–4344CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Balsalobre A, Damiola F, Schibler U (1998) A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93:929–937CrossRefPubMedGoogle Scholar
  11. 11.
    Balsalobre A, Marcacci L, Schibler U (2000) Multiple signaling pathways elicit circadian gene expression in cultured rat-1 fibroblasts. Curr Biol 10:1291–1294CrossRefPubMedGoogle Scholar
  12. 12.
    Vallone D, Gondi SB, Whitmore D, Foulkes NS (2004) E-box function in a period gene repressed by light. Proc Natl Acad Sci USA 101:4106–4111CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Vallone D, Santoriello C, Gondi SB, Foulkes NS (2007) Basic protocols for zebrafish cell lines: maintenance and transfection. Methods Mol Biol 362:429–441CrossRefPubMedGoogle Scholar
  14. 14.
    Carr A-JF, Whitmore D (2005) Imaging of single light-responsive clock cells reveals fluctuating free-running periods. Nat Cell Biol 7:319–321CrossRefPubMedGoogle Scholar
  15. 15.
    Shigeyoshi Y, Taguchi K, Yamamoto S, Takekida S, Yan L, Tei H et al (1997) Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript. Cell 91:1043–1053CrossRefPubMedGoogle Scholar
  16. 16.
    Wang H (2008) Comparative analysis of period genes in teleost fish genomes. J Mol Evol 67:29–40CrossRefPubMedGoogle Scholar
  17. 17.
    Wang H (2008) Comparative analysis of teleost fish genomes reveals preservation of different ancient clock duplicates in different fishes. Mar Genomics 1:69–78CrossRefPubMedGoogle Scholar
  18. 18.
    Wang H (2008) Comparative genomic analysis of teleost fish bmal genes. Genetica 136:149–161CrossRefPubMedGoogle Scholar
  19. 19.
    Liu C, Hu J, Qu C, Wang L, Huang G, Niu P et al (2015) Molecular evolution and functional divergence of zebrafish (Danio rerio) cryptochrome genes. Sci Rep 5:8113–8115CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kobayashi Y, Ishikawa T, Hirayama J, Daiyasu H, Kanai S, Toh H et al (2000) Molecular analysis of zebrafish photolyase/cryptochrome family: two types of cryptochromes present in zebrafish. Genes Cells 5:725–738CrossRefPubMedGoogle Scholar
  21. 21.
    Postlethwait JH, Yan Y-L, Gates MA, Horne S, Amores A, Brownlie A et al (1998) Vertebrate genome evolution and the zebrafish gene map. Nat Genet 18:345–349CrossRefPubMedGoogle Scholar
  22. 22.
    Ziv L, Gothilf Y (2006) Circadian time-keeping during early stages of development. Proc Natl Acad Sci 103:4146–4151CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tamai TK, Young LC, Whitmore D (2007) Light signaling to the zebrafish circadian clock by cryptochrome 1a. Proc Natl Acad Sci 104:14712–14717CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hirayama J, Fukuda I, Ishikawa T, Kobayashi Y, Todo T (2003) New role of zCRY and zPER2 as regulators of sub-cellular distributions of zCLOCK and zBMAL proteins. Nucleic Acids Res 31:935–943CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wang M, Zhong Z, Zhong Y, Zhang W, Wang H (2015) The zebrafish period2 protein positively regulates the circadian clock through mediation of retinoic acid receptor (RAR)-related orphan receptor α (Rorα). J Biol Chem 290:4367–4382CrossRefPubMedGoogle Scholar
  26. 26.
    Tamai TK, Vardhanabhuti V, Foulkes NS, Whitmore D (2004) Early embryonic light detection improves survival. Curr Biol 14:R104–R105CrossRefPubMedGoogle Scholar
  27. 27.
    Thompson CL, Sancar A (2002) Photolyase/cryptochrome blue-light photoreceptors use photon energy to repair DNA and reset the circadian clock. Oncogene 21:9043–9056CrossRefPubMedGoogle Scholar
  28. 28.
    Essen LO, Klar T (2006) Light-driven DNA repair by photolyases. Cell Mol Life Sci 63:1266–1277CrossRefPubMedGoogle Scholar
  29. 29.
    Fukushima N, Naito Y, Ryoji M (2009) Induction of (6-4) photolyase gene transcription by blue light in Xenopus A6 cells. Biochem Biophys Res Commun 383:231–234CrossRefPubMedGoogle Scholar
  30. 30.
    Yasuhira S, Yasui A (1992) Visible light-inducible photolyase gene from the goldfish Carassius auratus. J Biol Chem 267:25644–25647PubMedGoogle Scholar
  31. 31.
    Weger BD, Sahinbas M, Otto GW, Mracek P, Armant O, Dolle D et al (2011) The light responsive transcriptome of the zebrafish: function and regulation. PLoS ONE 6, e17080CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gavriouchkina D, Fischer S, Ivacevic T, Stolte J, Benes V, Dekens MPS (2010) Thyrotroph embryonic factor regulates light-induced transcription of repair genes in zebrafish embryonic cells. PLoS ONE 5, e12542CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Vatine G, Vallone D, Appelbaum L, Mracek P, Ben-Moshe Z, Lahiri K et al (2009) Light directs zebrafish period2 expression via conserved D and E boxes. PLoS Biol 7, e1000223CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mracek P, Santoriello C, Idda ML, Pagano C, Ben-Moshe Z, Gothilf Y et al (2012) Regulation of per and cry genes reveals a central role for the D-box enhancer in light-dependent gene expression. PLoS ONE 7, e51278CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Gachon F (2007) Physiological function of PARbZip circadian clock-controlled transcription factors. Ann Med 39:562–571CrossRefPubMedGoogle Scholar
  36. 36.
    Cowell IG (2002) E4BP4/NFIL3, a PAR-related bZIP factor with many roles. BioEssays: News Rev Mol Cell Dev Biol 24:1023–1029CrossRefGoogle Scholar
  37. 37.
    Ben-Moshe Z, Vatine G, Alon S, Tovin A, Mracek P, Foulkes NS et al (2010) Multiple PAR and E4BP4 bZIP transcription factors in zebrafish: diverse spatial and temporal expression patterns. Chronobiol Int 27:1509–1531CrossRefPubMedGoogle Scholar
  38. 38.
    Bowmaker JK (2008) Evolution of vertebrate visual pigments. Vis Res 48:2022–2041CrossRefPubMedGoogle Scholar
  39. 39.
    Davies WIL, Tamai TK, Zheng L, Fu JK, Rihel J, Foster RG et al (2015) An extended family of novel vertebrate photopigments is widely expressed and displays a diversity of function. Genome Res 25:1666–1679CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Pérez-Cerezales S, Boryshpolets S, Afanzar O, Brandis A, Nevo R, Kiss V et al (2015) Involvement of opsins in mammalian sperm thermotaxis. Sci Rep 5:16146CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Fain GL, Hardie R, Laughlin SB (2010) Phototransduction and the evolution of photoreceptors. Curr Biol 20:R114–R124CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hughes S, Hankins MW, Foster RG, Peirson SN 2012 Chapter 2 – Melanopsin phototransduction: slowly emerging from the dark. In: Andries Kalsbeek MMTR, Foster RG (eds) The neurobiology of circadian timing, vol 199. Elsevier, Amsterdam, the Netherlands, pp 19–40Google Scholar
  43. 43.
    Sexton T, Buhr E, Van Gelder RN (2012) Melanopsin and mechanisms of non-visual ocular photoreception. J Biol Chem 287:1649–1656CrossRefPubMedGoogle Scholar
  44. 44.
    Ramos BCR, Moraes MNCM, Poletini MO, Lima LHRG, Castrucci AML (2014) From blue light to clock genes in zebrafish ZEM-2S cells. PLoS ONE 9:e106252–12CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kawano T (2003) Roles of the reactive oxygen species-generating peroxidase reactions in plant defense and growth induction. Plant Cell Rep 21:829–837PubMedGoogle Scholar
  46. 46.
    Hockberger PE, Skimina TA, Centonze VE, Lavin C, Chu S, Dadras S et al (1999) Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells. Proc Natl Acad Sci U S A 96:6255–6260CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Osaki T, Uchida Y, Hirayama J, Nishina H (2011) Diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate oxidase, suppresses light-dependent induction of clock and DNA repair genes in zebrafish. Biol Pharm Bull 34:1343–1347CrossRefPubMedGoogle Scholar
  48. 48.
    Bolwell GP (1999) Role of active oxygen species and NO in plant defence responses. Curr Opin Plant Biol 2:287–294CrossRefPubMedGoogle Scholar
  49. 49.
    Bedard K, Krause K-H (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313CrossRefPubMedGoogle Scholar
  50. 50.
    Kamata H, Hirata H (1999) Redox regulation of cellular signalling. Cell Signal 11:1–14CrossRefPubMedGoogle Scholar
  51. 51.
    Hirayama J, Cho S, Sassone-Corsi P (2007) Circadian control by the reduction/oxidation pathway: catalase represses light-dependent clock gene expression in the zebrafish. Proc Natl Acad Sci 104:15747–15752CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Hall JC (2000) Cryptochromes: sensory reception, transduction, and clock functions subserving circadian systems. Curr Opin Neurobiol 10:456–466CrossRefPubMedGoogle Scholar
  53. 53.
    Oztürk N, Selby CP, Song S-H, Ye R, Tan C, Kao Y-T et al (2009) Comparative photochemistry of animal type 1 and type 4 cryptochromes. Biochemistry 48:8585–8593CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Wilkens H (2011) Variability and loss of functionless traits in cave animals. Reply to Jeffery (2010). Heredity 106:707–708CrossRefPubMedGoogle Scholar
  55. 55.
    Jeffery WR (2001) Cavefish as a model system in evolutionary developmental biology. Dev Biol 231:1–12CrossRefPubMedGoogle Scholar
  56. 56.
    Timmerman CM, Chapman LJ (2004) Behavioral and physiological compensation for chronic hypoxia in the sailfin molly (Poecilia latipinna). Physiol Biochem Zool 77:601–610CrossRefPubMedGoogle Scholar
  57. 57.
    Tobler M, Palacios M, Chapman LJ, Mitrofanov I, Bierbach D, Plath M et al (2011) Evolution in extreme environments: replicated phenotypic differentiation in livebearing fish inhabiting sulfidic springs. Evolution 65:2213–2228CrossRefPubMedGoogle Scholar
  58. 58.
    Beale A, Guibal C, Tamai TK, Klotz L, Cowen S, Peyric E et al (2013) Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field. Nat Commun 4:1–10CrossRefGoogle Scholar
  59. 59.
    Cavallari N, Frigato E, Vallone D, Fröhlich N, Lopez-Olmeda JF, Foà A et al (2011) A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception. PLoS Biol 9, e1001142CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Colli L, Paglianti A, Berti R, Gandolfi G, Tagliavini J (2009) Molecular phylogeny of the blind cavefish Phreatichthys andruzzii and Garra barreimiae within the family Cyprinidae. Environ Biol Fish 84:95–107CrossRefGoogle Scholar
  61. 61.
    Bradic M, Beerli P, García de León FJ, Esquivel-Bobadilla S, Borowsky RL (2012) Gene flow and population structure in the Mexican blind cavefish complex (Astyanax mexicanus). BMC Evol Biol 12:9CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Strecker U, Bernatchez L, Wilkens H (2003) Genetic divergence between cave and surface populations of Astyanax in Mexico (Characidae, Teleostei). Mol Ecol 12:699–710CrossRefPubMedGoogle Scholar

Copyright information

© Springer (India) Pvt. Ltd. 2017

Authors and Affiliations

  • Cristina Pagano
    • 1
  • Rosa Maria Ceinos
    • 1
  • Daniela Vallone
    • 1
  • Nicholas S. Foulkes
    • 1
  1. 1.Institute of Toxicology and GeneticsKarlsruhe Institute of TechnologyEggenstein-LeopoldshafenGermany

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