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The mammalian circadian timing system: from gene expression to physiology

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Abstract

Many physiological processes in organisms from bacteria to man are rhythmic, and some of these are controlled by self-sustained oscillators that persist in the absence of external time cues. Circadian clocks are perhaps the best characterized biological oscillators and they exist in virtually all light-sensitive organisms. In mammals, they influence nearly all aspects of physiology and behavior, including sleep-wake cycles, cardiovascular activity, endocrinology, body temperature, renal activity, physiology of the gastro-intestinal tract, and hepatic metabolism. The master pacemaker is located in the suprachiasmatic nuclei, two small groups of neurons in the ventral part of the hypothalamus. However, most peripheral body cells contain self-sustained circadian oscillators with a molecular makeup similar to that of SCN (suprachiasmatic nucleus) neurons. This organization implies that the SCN must synchronize countless subsidiary oscillators in peripheral tissues, in order to coordinate cyclic physiology. In this review, we will discuss some recent studies on the structure and putative functions of the mammalian circadian timing system, but we will also point out some apparent inconsistencies in the currently publicized model for rhythm generation.

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Acknowledgements

We would like to thank Nicolas Roggli for the artwork. Research from our own laboratory discussed in this review has been supported by Swiss National Science Foundation (grant to U.S.), the State of Geneva, the NCCR program “Frontiers in Genetics,” the Bonnizzi Theler Stiftung, and the Louis Jeantet Foundation of Medicine. F.G. received a postdoctoral fellowship from the Fondation pour la Recherche Médicale (France).

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  1. Department of Molecular Biology, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, 1211, Geneva-4, Switzerland

    Frédéric Gachon, Emi Nagoshi, Steven A. Brown, Juergen Ripperger & Ueli Schibler

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  1. Frédéric Gachon
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  2. Emi Nagoshi
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Correspondence to Ueli Schibler.

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Communicated by E.A. Nigg

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Gachon, F., Nagoshi, E., Brown, S.A. et al. The mammalian circadian timing system: from gene expression to physiology. Chromosoma 113, 103–112 (2004). https://doi.org/10.1007/s00412-004-0296-2

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