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Sci Rep. 2019 Jan 17;9(1):196. doi: 10.1038/s41598-018-37879-8.

The clock components Period2, Cryptochrome1a, and Cryptochrome2a function in establishing light-dependent behavioral rhythms and/or total activity levels in zebrafish.

Author information

1
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. jun.hirayama@komatsu-u.ac.jp.
2
Department of Clinical Engineering, Faculty of Health Sciences, Komatsu University, Ishikawa, Japan. jun.hirayama@komatsu-u.ac.jp.
3
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
4
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
5
Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University (TMDU), Ichikawa, Japan.
6
Department of Microbiology and Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
7
Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
8
Department of Physiology and Advanced Research Center for Medical Science, Toho University School of Medicine, Tokyo, Japan.
9
Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan.
10
Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development, Tokyo, Japan.
11
Laboratory for Developmental Biology, Center for Medical Education and Sciences, Graduate School of Medical Science, University of Yamanashi, Yamanashi, Japan.
12
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. kume@phar.nagoya-cu.ac.jp.
13
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. nishina.dbio@mri.tmd.ac.jp.

Abstract

The circadian clock generates behavioral rhythms to maximize an organism's physiological efficiency. Light induces the formation of these rhythms by synchronizing cellular clocks. In zebrafish, the circadian clock components Period2 (zPER2) and Cryptochrome1a (zCRY1a) are light-inducible, however their physiological functions are unclear. Here, we investigated the roles of zPER2 and zCRY1a in regulating locomotor activity and behavioral rhythms. zPer2/zCry1a double knockout (DKO) zebrafish displayed defects in total locomotor activity and in forming behavioral rhythms when briefly exposed to light for 3-h. Exposing DKO zebrafish to 12-h light improved behavioral rhythm formation, but not total activity. Our data suggest that the light-inducible circadian clock regulator zCRY2a supports rhythmicity in DKO animals exposed to 12-h light. Single cell imaging analysis revealed that zPER2, zCRY1a, and zCRY2a function in synchronizing cellular clocks. Furthermore, microarray analysis of DKO zebrafish showed aberrant expression of genes involved regulating cellular metabolism, including ATP production. Overall, our results suggest that zPER2, zCRY1a and zCRY2a help to synchronize cellular clocks in a light-dependent manner, thus contributing to behavioral rhythm formation in zebrafish. Further, zPER2 and zCRY1a regulate total physical activity, likely via regulating cellular energy metabolism. Therefore, these circadian clock components regulate the rhythmicity and amount of locomotor behavior.

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