Peripheral clocks tick independently of their master

Abstract

The circadian system of mammals is hierarchically organized. The suprachiasmatic nucleus (SCN) in the hypothalamus is considered the master circadian clock adapting to environmental light-dark cycles and synchronizing subsidiary oscillators in peripheral organs. While being an attractive concept, this has never been convincingly shown in vivo. New findings by Sinturel and colleagues (pp. 329-334) in this issue of Genes & Development now show the requirement of the SCN for temporal orchestration of the periphery in living animals. Surprisingly, this study also found that even in the absence of SCN or extra-SCN clocks, peripheral clocks remain rhythmic, indicating previously controversial circadian oscillator coupling within peripheral tissues.

Figure 1.

Organization of the mammalian circadian system. The circadian system in mammals consists of multiple body clocks. The suprachiasmatic nucleus (SCN) in the hypothalamus constitutes a highly robust oscillator network due to intercellular neurotransmitter coupling. (GABA) γ-Aminobutyric acid, (AVP) arginine vasopressin, (VIP) vasoactive intestinal polypeptide. It receives photic entrainment signals from the environment, which are transmitted via multiple behavioral and (neuro-)endocrine pathways, to peripheral body clocks in order to align them with the external light–dark cycle, as well as with each other. Peripheral oscillators constitute weakly coupled, yet autonomous, body clocks that drive rhythmic tissue functions. Whether peripheral clocks exchange mutual or peripheral-to-central feedback signals, as well as which factors mediate intercellular coupling within peripheral tissues, is currently unknown.