Clock-Talk: Interactions between Central and Peripheral Circadian Oscillators in Mammals
- Ueli Schibler1,
- Ivana Gotic1,
- Camille Saini1,2,
- Pascal Gos1,
- Thomas Curie3,
- Yann Emmenegger3,
- Flore Sinturel1,
- Pauline Gosselin1,
- Alan Gerber1,4,
- Fabienne Fleury-Olela1,
- Gianpaolo Rando1,
- Maud Demarque1 and
- Paul Franken3
- 1Department of Molecular Biology, University of Geneva, CH-1211 Geneva, Switzerland
- 2Laboratory of Circadian Endocrinology, Geneva University Hospitals, CH-1205 Geneva, Switzerland
- 3Center of Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland
- 4Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10065
- Correspondence: ueli.schibler{at}unige.ch
Abstract
In mammals, including humans, nearly all physiological processes are subject to daily oscillations that are governed by a circadian timing system with a complex hierarchical structure. The central pacemaker, residing in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus, is synchronized daily by photic cues transmitted from the retina to SCN neurons via the retinohypothalamic tract. In turn, the SCN must establish phase coherence between self-sustained and cell-autonomous oscillators present in most peripheral cell types. The synchronization signals (Zeitgebers) can be controlled more or less directly by the SCN. In mice and rats, feeding–fasting rhythms, which are driven by the SCN through rest–activity cycles, are the most potent Zeitgebers for the circadian oscillators of peripheral organs. Signaling through the glucocorticoid receptor and the serum response factor also participate in the phase entrainment of peripheral clocks, and these two pathways are controlled by the SCN independently of feeding–fasting rhythms. Body temperature rhythms, governed by the SCN directly and indirectly through rest–activity cycles, are perhaps the most surprising cues for peripheral oscillators. Although the molecular makeup of circadian oscillators is nearly identical in all cells, these oscillators are used for different purposes in the SCN and in peripheral organs.
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