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Circadian clock system in the pineal gland

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Abstract

The pineal gland is a neuroendocrine organ that functions as a central circadian oscillator in a variety of nonmammalian vertebrates. In many cases, the pineal gland retains photic input and endocrinal-output pathways both linked tightly to the oscillator. This contrasts well with the mammalian pineal gland equipped only with the output of melatonin production that is subject to neuronal regulation by central circadian oscillator located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Molecular studies on animal clock genes were performed first in Drosophila and later developed in rodents. More recently, clock genes such as Per, Cry, Clock, and Bmal have been found in a variety of vertebrate clock structures including the avian pineal gland. The profiles of the temporal change of the clock gene expression in the avian pineal gland are more similar to those in the mammalian SCN rather than to those in the mammalian pineal gland. Avian pineal gland and mammalian SCN seem to share a fundamental molecular framework of the clock oscillator composed of a transcription/translation-based autoregulatory feedback loop. The circadian time-keeping mechanism also requires several post-translational events, such as protein translocation and degradation processes, in which protein phosphorylation plays a very important role for the stable 24-h cycling of the oscillator and/or the photic-input pathway for entrainment of the clock.

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References

  1. King D. P. and Takahashi J. S. (2000) Molecular genetics of circadian rhythms in mammals. Annu. Rev. Neurosci. 23, 713–742.

    Article  PubMed  CAS  Google Scholar 

  2. Deguchi T. (1979) Circadian rhythm of serotonin-N-acetyltransferase activity in organ culture of chicken pineal gland. Science 203, 1245–1247.

    Article  PubMed  CAS  Google Scholar 

  3. Kasal C. H., Menaker M., and Perez-Polo J. R. (1979) Circadian clock in culture: N-acetyltransferase activity of chick pineal glands oscillates in vitro. Science 203, 656–658.

    Article  PubMed  CAS  Google Scholar 

  4. Zatz M., Mullen D. A., and Moskal J. R. (1988) Photoendocrine transduction in cultured chick pineal cells: effects of light, dark, and potassium on the melatonin rhythm. Brain Res. 438, 199–215.

    Article  PubMed  CAS  Google Scholar 

  5. Cahill G. M. and Besharse J. C. (1993) Circadian clock functions localized in Xenopus retinal photoreceptors. Neuron 10, 573–577.

    Article  PubMed  CAS  Google Scholar 

  6. Klein D. C., Coon S. L., Roseboom P. H., Weller J. L., Bernard M., Gastel J. A., et al. (1997) The melatonin rhythm-generating enzyme: molecular regulation of serotonin-N-acetyltransferase in the pineal gland. Recent Prog. Horm. Res. 52, 307–358.

    PubMed  CAS  Google Scholar 

  7. Zatz M., Gastel J. A., Heath III J. R., and Klein D. C. (2000) Chick pineal melatonin synthesis: light and cyclic AMP control abundance of serotonin N-acetyltransferase protein. J. Neurochem. 74, 2315–2321.

    Article  PubMed  CAS  Google Scholar 

  8. Yoshimura T., Yasuo S., Suzuki Y., Makino E., Yokota Y., and Ebihara S. (2001) Identification of the suprachiasmatic nucleus in birds. Am. J. Physiol. 280, R1185-R1189.

    CAS  Google Scholar 

  9. Kuenzel W. J. (1993) The search for deep encephalic photoreceptors within the avian brain, using gonadal development as a primary indicator. Poult. Sci. 72, 959–967.

    PubMed  CAS  Google Scholar 

  10. Okano T., Yoshizawa T., and Fukada Y. (1994) Pinopsin is a chicken pineal photoreceptive molecule. Nature 372, 94–97.

    Article  PubMed  CAS  Google Scholar 

  11. Blackshaw S. and Snyder S. H. (1997) Parapinopsin, a novel catfish opsin localized to the parapineal organ, defines a new gene family. J. Neurosci. 17, 8083–8092.

    PubMed  CAS  Google Scholar 

  12. Soni B. G. and Foster R. G. (1997) A novel and ancient vertebrate opsin. FEBS Lett. 406, 279–283.

    Article  PubMed  CAS  Google Scholar 

  13. Provencio I., Jiang G., De Grip W. J., Hayes W. P., and Rollag M. D. (1998) Melanopsin: An opsin in melanophores, brain, and eye. Proc. Natl. Acad. Sci. USA 95, 340–345.

    Article  PubMed  CAS  Google Scholar 

  14. Wada Y., Okano T., Adachi A., Ebihara S., and Fukada Y. (1998) Identification of rhodopsin in the pigeon deep brain. FEBS Lett. 424, 53–56.

    Article  PubMed  CAS  Google Scholar 

  15. Yoshikawa T., Okano T., Oishi T., and Fukada Y. (1998) A deep brain photoreceptive molecule in the toad hypothalamus. FEBS Lett. 424, 69–72.

    Article  PubMed  Google Scholar 

  16. Mano H., Kojima D., and Fukada Y. (1999) Exorhodopsin: a novel rhodopsin expressed in the zebrafish pineal gland. Mol. Brain Res., 73, 110–118.

    Article  PubMed  CAS  Google Scholar 

  17. Kojima D., Mano H., and Fukada Y. (2000) Vertebrate ancient-long opsin: a green-sensitive photoreceptive molecule present in zebrafish deep brain and retinal horizontal cells. J. Neurosci. 20, 2845–2851.

    PubMed  CAS  Google Scholar 

  18. Okano T. and Fukada Y. (2001) Photoreception and circadian clock system of the chicken pineal gland. Microscopy Res. Technique 53, 72–80.

    Article  CAS  Google Scholar 

  19. Kasahara T., Okano T., Yoshikawa T., Yamazaki K., and Fukada Y. (2000) Rod-type transducin α-subunit mediates a phototransduction pathway in the chicken pineal gland. J. Neurochem. 75, 217–224.

    Article  PubMed  CAS  Google Scholar 

  20. Wada Y., Okano T., and Fukada Y. (2000) Phototransduction molecules in the pigeon deep brain. J. Comp. Neurol. 428, 138–144.

    Article  PubMed  CAS  Google Scholar 

  21. Hamasaki D. I. and Eder D. J. (1977) Adaptive radiation of the pineal system, in The Visual System in Vertebrates, Handbook of Sensory Physiology, vol. VII/5, (Crescitelli F., ed.), Springer-Verlag, NY, pp. 497–548.

    Google Scholar 

  22. Janik D. S. and Menaker M. (1990) Circadian locomotor rhythms in the desert iguana. I. The role of the eyes and the pineal. J. Comp. Physiol. 166, 803–810.

    CAS  Google Scholar 

  23. Cahill G. M. (1996) Circadian regulation of melatonin production in cultured zebrafish pineal and retina. Brain Res. 708, 177–181.

    Article  PubMed  CAS  Google Scholar 

  24. Schomerus C., Korf H.-W., Laedtke E., Weller J. L., and Klein D. C. (2000) Selective adrenergic/cyclic AMP-dependent switch-off of proteasomal proteolysis alone switches on neural signal transduction: an example from the pineal gland. J. Neurochem. 75, 2123–2132.

    Article  PubMed  CAS  Google Scholar 

  25. Deguchi T. (1979) Role of adenosine 3′.5′-monophosphate in the regulation of circadian oscillation of serotonin N-acetyltransferase activity in cultured chicken pineal gland. J. Neurochem. 33, 45–51.

    Article  PubMed  CAS  Google Scholar 

  26. Takahashi J. S., Murakami N., Nikaido S. S., Pratt B. L., and Robertson L. M. (1989) The avian pineal, a vertebrate model system of the circadian oscillator. Recent Prog. Horm. Res. 45, 279–352.

    PubMed  CAS  Google Scholar 

  27. Nakahara K., Murakami N., Nasu T., Kuroda H., and Murakami T. (1997) Individual pineal cells in chick possess photoreceptive, circadian clock and melatonin-synthesizing capacities in vitro. Brain Res. 774, 242–245.

    Article  PubMed  CAS  Google Scholar 

  28. Okano T. and Fukada Y. (1997) Phototransduction cascade and circadian oscillator in chicken pineal gland. J. Pineal Res. 22, 145–151.

    Article  PubMed  CAS  Google Scholar 

  29. Yoshimura T., Suzuki Y., Makino E., Suzuki T., Kuroiwa A., Matsuda Y., et al. (2000) Molecular analysis of avian circadian clock genes. Mol. Brain Res. 78, 207–215.

    Article  PubMed  CAS  Google Scholar 

  30. Okano T., Yamamoto K., Okano K., Hirota T., Kasahara T., Sasaki M., et al. (2001) Chicken pineal clock genes: implication of BMAL2 as a bidirectional regulator in circadian clock oscillation. Genes Cells 6, 825–836.

    Article  PubMed  CAS  Google Scholar 

  31. Yamamoto K., Okano T., and Fukada Y. (2001) Chicken pineal Cry genes: light-dependent up-regulation of cCry1 and cCry2 transcripts. Neurosci. Lett. 313, 13–16.

    Article  PubMed  CAS  Google Scholar 

  32. Dunlap J. C. (1999) Molecular bases for circadian clock. Cell 96, 271–290.

    Article  PubMed  CAS  Google Scholar 

  33. Hardin P. E. and Glossop N. R. (1999) The CRYs of flies and mice. Science 286, 2460–2461.

    Article  PubMed  CAS  Google Scholar 

  34. Young M. W. (2000) Life’s 24-hour clock: molecular control of circadian rhythms in animal cells. Trends Biochem. Sci. 25, 601–605.

    Article  PubMed  CAS  Google Scholar 

  35. Gekakis N., Staknis D., Nguyen H. B., Davis F. C., Wilsbacher L. D., King D. P., et al. (1998) Role of the CLOCK protein in the mammalian circadian mechanism. Science 280, 1564–1569.

    Article  PubMed  CAS  Google Scholar 

  36. Jin X., Shearman L. P., Weaver D. R., Zylka M. J., de Vries G. J., and Reppert S. M. (1999) A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96, 57–68.

    Article  PubMed  CAS  Google Scholar 

  37. Chong N. W., Bernard M., and Klein D. C. (2000) Characterization of the chicken serotonin N-acetyltransferase gene. J. Biol. Chem. 275, 32,991–32,998.

    Article  CAS  Google Scholar 

  38. Ripperger J. A., Shearman L. P., Reppert S. M., and Schibler U. (2000) CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes Dev. 14, 679–689.

    PubMed  CAS  Google Scholar 

  39. Shearman L. P., Sriram S., Weaver D. R., Maywood E. S., Chaves I., Zheng B., et al. (2000) Interacting molecular loops in the mammalian circadian clock. Science 288, 1013–1019.

    Article  PubMed  CAS  Google Scholar 

  40. Honma S., Ikeda M., Abe H., Tanahashi Y., Namihira M., Honma K., and Nomura M. (1998) Circadian oscillation of BMAL1, a partner of a mammalian clock gene Clock, in rat suprachiasmatic nucleus. Biochem. Biophys. Res. Commun. 250, 83–87.

    Article  PubMed  CAS  Google Scholar 

  41. Oishi K., Sakamoto K., Okada T., Nagase T., and Ishida N. (1998) Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats. Biochem. Biophys. Res. Commun. 253, 199–201.

    Article  PubMed  CAS  Google Scholar 

  42. Namihira M., Honma S., Abe H., Tanahashi Y., Ikeda M., Honma K. (1999) Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats. Neurosci. Lett. 267, 69–72.

    Article  PubMed  CAS  Google Scholar 

  43. Clayton J. D., Kyriacou C. P., and Reppert S. M. (2001) Keeping time with the human genome. Nature 409, 829–831.

    Article  PubMed  CAS  Google Scholar 

  44. Albrecht U., Sun Z. S., Eichele G., and Lee C. C. (1997). A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light. Cell 91, 1055–1064.

    Article  PubMed  CAS  Google Scholar 

  45. Shearman L. P., Zylka M. J., Weaver D. R., Kolakowski L. F. Jr, Reppert S. M. (1997) Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron 19, 1261–1269.

    Article  PubMed  CAS  Google Scholar 

  46. Sun Z. S., Albrecht U., Zhuchenko O., Bailey J., Eichele G., and Lee C. C. (1997) RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 90, 1003–1011.

    Article  PubMed  CAS  Google Scholar 

  47. Tei H., Okamura H., Shigeyoshi Y., Fukuhara C., Ozawa R., Hirose M., and Sakaki Y. (1997) Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature 389, 512–516.

    Article  PubMed  CAS  Google Scholar 

  48. Takumi T., Matsubara C., Shigeyoshi Y., Taguchi K., Yagita K., Maebayashi Y., et al. (1998) A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus. Genes Cells 3, 167–176.

    Article  PubMed  CAS  Google Scholar 

  49. Takumi T., Taguchi K., Miyake S., Sakakida Y., Takashima N., Matsubara C., et al. (1998) A light-independent oscillatory gene mPer3 in mouse SCN and OVLT. EMBO J. 17, 4753–4759.

    Article  PubMed  CAS  Google Scholar 

  50. Zylka M. J., Shearman L. P., Weaver D. R., and Reppert S. M. (1998) Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron 20, 1103–1110.

    Article  PubMed  CAS  Google Scholar 

  51. Delaunay F., Thisse C., Marchand O., Laudet V., and Thisse B. (2000) An inherited functional circadian clock in zebrafish embryos. Science 289, 297–300.

    Article  PubMed  CAS  Google Scholar 

  52. Zhuang M., Wang Y., Steenhard B. M., and Besharse J. C. (2000) Differential regulation of two Period genes in the Xenopus eye. Mol. Brain Res. 82, 52–64.

    Article  PubMed  CAS  Google Scholar 

  53. Fukuhara C., Dirden J. C., and Tosini G. (2000) Circadian expression of Period1, Period 2, and Arylalkylamine N-acetyltransferase mRNA in the rat pineal gland under different light conditions. Neurosci. Lett. 286, 167–170.

    Article  PubMed  CAS  Google Scholar 

  54. Takekida S., Yan L., Maywood E. S., Hastings M. H., and Okamura H. (2000) Differential adrenergic regulation of the circadian expression of the clock genes Period1 and Period2 in the rat pineal gland. Eur. J. Neurosci. 12, 4557–4561.

    Article  PubMed  CAS  Google Scholar 

  55. Yamazaki S., Numano R., Abe M., Hida A., Takahashi R., Ueda M., et al. (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288, 682–685.

    Article  PubMed  CAS  Google Scholar 

  56. 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, 1043–1053.

    Article  PubMed  CAS  Google Scholar 

  57. Bernard M., Iuvone P. M., Cassone V. M., Roseboom P. H., Coon S. L. and Klein D. C. (1997). Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina. J. Neurochem. 68, 213–224.

    Article  PubMed  CAS  Google Scholar 

  58. Stanewsky R., Kaneko M., Emery P., Beretta B., Wager-Smith K., Kay S. A., et al. (1998) The cry b mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95, 681–692.

    Article  PubMed  CAS  Google Scholar 

  59. Kume K., Zylka M. J., Sriram S., Shearman L. P., Weaver D. R., Jin X., et al. (1999) mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98, 193–205.

    Article  PubMed  CAS  Google Scholar 

  60. van der Horst G. T., Muijtjens M., Kobayashi K., Takano R., Kanno S., Takao M., et al. (1999) Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398, 627–630.

    Article  PubMed  Google Scholar 

  61. 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, 725–738.

    Article  PubMed  CAS  Google Scholar 

  62. Miyamoto Y. and Sancar A. (1998) Vitamin B2-based blue-light photoreceptors in the retinohy-pothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc. Natl. Acad. Sci. USA 95, 6097–6102.

    Article  PubMed  CAS  Google Scholar 

  63. Okamura H., Miyake S., Sumi Y., Yamaguchi S., Yasui A., Muijtjens M., et al. (1999) Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science 286, 2531–2534.

    Article  PubMed  CAS  Google Scholar 

  64. Antoch M. P., Song E. J., Chang A. M., Vitatema M. H., Zhao Y., Wilsbacher L. D., et al. (1997) Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89, 655–667.

    Article  PubMed  CAS  Google Scholar 

  65. King D. P., Zhao Y., Sangoram A. M., Wilsbacher L. D., Tanaka M., Antoch M. P., et al. (1997) Positional cloning of the mouse circadian Clock gene. Cell 89, 641–653.

    Article  PubMed  CAS  Google Scholar 

  66. Zhou Y.-D., Barnard M., Tian H., Li X., Ring H. Z., Francke U., et al. (1997) Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. Proc. Natl. Acad. Sci. USA 94, 713–718.

    Article  PubMed  CAS  Google Scholar 

  67. Hogenesch J. B., Gu Y. Z., Jain S., and Bradfield C. A. (1998) The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc. Natl. Acad. Sci. USA 95, 5474–5479.

    Article  PubMed  CAS  Google Scholar 

  68. Reick M., Garcia J. A., Dudley C., and McKnight S. L. (2001) NPAS2: An analog of clock operative in the mammalian forebrain. Science 293, 506–509.

    Article  PubMed  CAS  Google Scholar 

  69. Abe H., Honma S., Namihira M., Tanahashi Y., Ikeda M., Yu W. and Honma K. (1999) Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus. Mol. Brain Res. 66, 104–110.

    Article  PubMed  CAS  Google Scholar 

  70. Larkin P., Baehr W., and Semple-Rowland S. L. (1999) Circadian regulation of iodopsin and clock is altered in the retinal degeneration chicken retina. Mol. Brain Res. 70, 253–263.

    Article  PubMed  CAS  Google Scholar 

  71. Ikeda M. and Nomura M. (1997) cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage. Biochem. Biophys. Res. Commun. 233, 258–264.

    Article  PubMed  CAS  Google Scholar 

  72. Bunger M. K., Wilsbacher L. D., Moran S. M., Clendenin C., Radcliffe L. A., Hogenesch J. B., et al. (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103, 1009–1017.

    Article  PubMed  CAS  Google Scholar 

  73. Cermakian N., Whitmore D., Foulkes N. S., and Sassone-Corsi P. (2000). Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function. Proc. Natl. Acad. Sci. USA 97, 4339–4344.

    Article  PubMed  CAS  Google Scholar 

  74. Ikeda M., Yu W., Hirai M., Ebisawa T., Honma S., Yoshimura K., et al. (2000) cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2: its mRNA expression, subcellular distribution, and chromosomal localization. Biochem. Biophys. Res. Commun. 275, 493–502.

    Article  PubMed  CAS  Google Scholar 

  75. Okano T., Sasaki M., and Fukada Y. (2001) Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication. Neurosci. Lett. 300, 111–114.

    Article  PubMed  CAS  Google Scholar 

  76. Maemura K., de la Monte S. M., Chin M. T., Layne M. D., Hsieh C. M., Yet S. F., et al. (2000) CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression. J. Biol. Chem. 275, 36,847–36,851.

    Article  CAS  Google Scholar 

  77. Hogenesch J. B., Gu Y. Z., Moran S. M., Shimomura K., Radcliffe L. A., Takahashi J. S., and Bradfield C. A. (2000) The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors. J. Neurosci. 20, RC83.

    Google Scholar 

  78. Yamaguchi S., Mitsui S., Yan L., Yagita K., Miyake S., and Okamura H. (2000) Role of DBP in the circadian oscillatory mechanism. Mol. Cell. Biol. 13, 4773–4781.

    Article  Google Scholar 

  79. Doi M., Nakajima Y., Okano T., and Fukada Y. (2001) Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene. Proc. Natl. Acad. Sci. USA 98, 8089–8094.

    Article  PubMed  CAS  Google Scholar 

  80. Mitsui S., Yamaguchi S., Matsuo T., Ishida Y., and Okamura H. (2001) Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev. 15, 995–1006.

    Article  PubMed  CAS  Google Scholar 

  81. Blau J., and Young M. W. (1999) Cycling vrille expression is required for a functional Drosophila clock. Cell 99, 661–671.

    Article  PubMed  CAS  Google Scholar 

  82. Kloss B., Price J. L., Saez L., Blau J., Rothenfluh A., Wesley C. S., and Young M. W. (1998) The Drosophila clock gene double-time encodes a protein closely related to human casein-kinase lε. Cell 94, 97–107.

    Article  PubMed  CAS  Google Scholar 

  83. Price J. L., Blau J., Rothenfluh A., Abodeely M., Kloss B., and Young M. W. (1998) Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94, 83–95.

    Article  PubMed  CAS  Google Scholar 

  84. Lowrey P. L., Shimomura K., Antoch M. P., Yamazaki S., Zemenides P. D., Ralph M. R., et al. (2000) Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science 288, 483–492.

    Article  PubMed  CAS  Google Scholar 

  85. Vielhaber E., Eide E., Rivers A., Gao Z. H., and Virshup D. M. (2000) Nuclear entry of the circadian regulator mPer1 is controlled by mammalian casein kinase lε. Mol. Cell Biol. 20, 4888–4899.

    Article  PubMed  CAS  Google Scholar 

  86. Takano A., Shimizu K., Kani S., Buijs R. M., Okada M., and Nagai K. (2000) Cloning and characterization of rat casein kinase lε FEBS Lett. 477, 106–112.

    Article  PubMed  CAS  Google Scholar 

  87. Obrietan K., Impey S., and Storm D. R. (1998) Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei. Nat. Neurosci. 1, 693–700.

    Article  PubMed  CAS  Google Scholar 

  88. Sanada K., Hayashi Y., Harada Y., Okano T., and Fukada Y. (2000) Role of circadian activation of mitogen-activated protein kinase in chick pineal clock oscillation. J. Neurosci. 20, 986–991.

    PubMed  CAS  Google Scholar 

  89. Harada Y., Sanada K., and Fukada Y. (2000). Circadian activation of bullfrog retinal mitogen-activated protein kinase associates with oscillator function. J. Biol. Chem. 275, 37,078–37,085.

    CAS  Google Scholar 

  90. Ko G. Y., Ko M. L., and Dryer S. E. (2001) Circadian regulation of cGMP-gated cationic channels of chick retinal cones. Erk MAP kinase and Ca2+/calmodulin-dependent protein kinase II. Neuron 29, 255–266.

    Article  PubMed  CAS  Google Scholar 

  91. Hayashi Y., Sanada K., and Fukada Y. (2001) Circadian and photic regulation of MAP kinase by Ras- and protein phosphatase-dependent pathway in the chicken pineal gland. FEBS Lett. 491, 71–75.

    Article  PubMed  CAS  Google Scholar 

  92. Sanada, K., Okano, T., and Fukuda, Y. (2002) Mitogen activated protein kinase phosphorylates and negatively regulates basic helix-loop-helix-PAS transcription factor BMAL1. J. Biol. Chem. 277, 267–271.

    Article  PubMed  CAS  Google Scholar 

  93. Akiyama M., Kouzu Y., Takahashi S., Wakamatsu H., Moriya T., Maetani M., Watanabe S., et al. (1999). Inhibition of light-or glutamate-induced mPer1 expression represses the phase shifts into the mouse circadian locomotor and suprachiasmatic firing rhythms. J. Neurosci. 19, 1115–1121.

    PubMed  CAS  Google Scholar 

  94. Matsushita A., Yoshikawa T., Okano T., Kasahara T., and Fukada Y. (2000) Colocalization of pinopsin with two types of G-protein α-subunits in the chicken pineal gland. Cell Tissue Res. 299, 245–251.

    PubMed  CAS  Google Scholar 

  95. Zhu H., LaRue S., Whiteley A., Steeves T. D. L., Takahashi J. S., and Green C. B. (2000) The Xenopus Clock gene is constitutively expressed in retinal photoreceptors. Mol. Brain Res. 75, 303–308.

    Article  PubMed  CAS  Google Scholar 

  96. Whitmore D., Foulkes N. S., Strahle U., and Sassone-Corsi P. (1998) Zebrafish clock rhythmic expression reveals independent peripheral circadian oscillators. Nat. Neurosci. 1, 701–707.

    Article  PubMed  CAS  Google Scholar 

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Fukada, Y., Okano, T. Circadian clock system in the pineal gland. Mol Neurobiol 25, 19–30 (2002). https://doi.org/10.1385/MN:25:1:019

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