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Zebrafish Clock rhythmic expression reveals independent peripheral circadian oscillators

Abstract

The only vertebrate clock gene identified by mutagenesis is mouse Clock , which encodes a bHLH-PAS transcription factor. We have cloned Clock in zebrafish and show that, in contrast to its mouse homologue, it is expressed with a pronounced circadian rhythm in the brain and in two defined pacemaker structures, the eye and the pineal gland. Clock oscillation was also found in other tissues, including kidney and heart. In these tissues, expression of Clock continues to oscillate in vitro . This demonstrates that self-sustaining circadian oscillators exist in several vertebrate organs, as was previously reported for invertebrates.

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Figure 1: Conservation of zebrafish, mouse and Drosophila CLOCK.
Figure 2: Expression of the zebrafish Clock gene oscillates in pacemaker structures.
Figure 3: Clock expression oscillates in the zebrafish brain.
Figure 4: Clock expression in different zebrafish organs demonstrates the existence of independent circadian oscillators.

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Acknowledgements

We thank Joseph S. Takahashi, Nicolas Cermakian, Dario De Cesare, Lucia Monaco, Jean-Marie Garnier, Pilar Garcia-Villalba and Patrick Blader for discussions, advice and gifts of materials. We also acknowledge the technical assistance of Estelle Heitz, as well as Dominique Biellman, Odile Nkundwa, Nadine Fisher, Serge Vicaire and Frank Ruffenach. D.W. was supported by an EEC TMR fellowship. Our studies are funded by grants from CNRS, INSERM, CHUR, Rhône-Poulenc Rorer (Bioavenir), Fondation pour la Recherche Médicale and Association pour la Recherche sur le Cancer (P. S.-C.).

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Correspondence to Paolo Sassone-Corsi.

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Whitmore, D., Foulkes, N., Strähle, U. et al. Zebrafish Clock rhythmic expression reveals independent peripheral circadian oscillators. Nat Neurosci 1, 701–707 (1998). https://doi.org/10.1038/3703

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