Clock Hierarchy

Abstract

The mammalian circadian system comprises central and peripheral circadian clocks, the former localized within the suprachiasmatic nucleus (SCN) of the hypothalamus and the latter present in numerous peripheral tissues such as the muscle and liver. However, SCN-derived signals are thought to control peripheral tissue oscillations, and it has been difficult to understand this communication at a molecular level. Pando et al . show that dominance of the SCN clock is observed in a tissue implant system in which embryonic fibroblasts from one mouse (Mefs) are placed into the back of a genetically different host mouse. Mefs taken from a mouse that lacks the clock transcription factor Per1, a defect known not to affect oscillations in the SCN, displayed shorter oscillation periods in culture than did cells from wild-type mice. However, when transplanted into a wild-type mouse, the Per1-null Mefs adopted the normal oscillatory phenotype of the host SCN. When transplanted into a mouse with a longer oscillation period, the Mefs adopted those characteristics as well. The Mefs were only influenced by the host SCN if they expressed other functional clock components, suggesting that cues from the central pacemaker are interpreted by the implant's clock. This system may allow genetic and molecular dissection of what SCN signals initiate and maintain oscillations in implanted peripheral clocks and may also help address whether and how peripheral clocks are uncoupled from the central clock in response to certain environmental cues such as food intake. M. P. Pando, D. Morse, N. Cermakian, P. Sassone-Corsi, Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance. Cell 110 , 107-117 (2002). [Online Journal]