Published online: 21 October 2007; | doi:10.1038/ncb1653
Melanopsin-dependent photo-perturbation reveals desynchronization underlying the singularity of mammalian circadian clocksHideki Ukai1, 9, Tetsuya J. Kobayashi1, 4, 9, Mamoru Nagano5, Koh-hei Masumoto1, Mitsugu Sujino5, Takao Kondo6, Kazuhiro Yagita7, 8, Yasufumi Shigeyoshi5 & Hiroki R. Ueda1, 21
Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. 2
Functional Genomics Unit, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. 3
Department of Bioscience, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan. 4
Research Fellow of Japan Society for the Promotion of Science, Kinki University School of Medicine, 377-2 Ohno-Hagashi, Osaka-Sayama, Osaka 589-8511, Japan. 5
Department of Anatomy and Neurobiology, Kinki University School of Medicine, 377-2 Ohno-Hagashi, Osaka-Sayama, Osaka 589-8511, Japan. 6
Division of Biological Science, Graduate School of Science, Nagoya University and CREST & SORST, Japan Science and Technology Corporation, Furo-cho 1, Chikusa, Nagoya 464-8602, Japan. 7
COE Unit of Circadian Systems, Division of Molecular Genetics, Department of Biological Sciences, Nagoya University Graduate School of Science, Furo-cho, Chikusa-ku, Nagoya, 464-8602, Japan. 8
Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 9
These authors contributed equally to this work.
Correspondence should be addressed to Hiroki R. Ueda uedah-tky@umin.ac.jp Singularity behaviour in circadian clocks1,
2 — the loss of robust circadian rhythms following exposure to a stimulus such as a pulse of bright light — is one of the fundamental but mysterious properties of clocks. To quantitatively perturb and accurately measure the dynamics of cellular clocks3,
4, we synthetically produced photo-responsiveness within mammalian cells by exogenously introducing the photoreceptor melanopsin5,
6,
7,
8 and continuously monitoring the effect of photo-perturbation on the state of cellular clocks. Here we report that a critical light pulse drives cellular clocks into singularity behaviour. Our theoretical analysis consistently predicts and subsequent single-cell level observation directly proves that desynchronization of individual cellular clocks underlies singularity behaviour. Our theoretical framework also explains why singularity behaviours have been experimentally observed in various organisms, and it suggests that desynchronization is a plausible mechanism for the observable singularity of circadian clocks. Importantly, these in vitro and in silico findings are further supported by in vivo observations that desynchronization underlies the multicell-level amplitude decrease in the rat suprachiasmatic nucleus induced by critical light pulses.
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