On the communication pathways between the central pacemaker and peripheral oscillators.

Circadian rhythms are regulated by clocks located in specific structures of the CNS, such as the suprachiasmatic nucleus (SCN) in mammals, and by peripheral oscillators present in various other tissues. The expression of essential clock genes oscillates both in the SCN and in peripheral pacemakers. Peripheral tissues in the fly and in the fish are directly photoreceptive. In particular, we have established the Z3 embryonic zebrafish cell line that recapitulates the dynamic light-dependent regulation of the vertebrate clock in vitro. In mammals the synchronization to daily light cycles involves neural connections from a subset of light-sensitive receptor-containing retinal ganglion cells. Humoral and/or hormonal signals originating from the SCN are thought to provide timing cues to peripheral clocks. However, alternative routes exist, as some peripheral clocks in mammals can be specifically entrained in a SCN-independent manner by restricted feeding regimes. Thus, not all peripheral tissues are equal in circadian rhythmicity. Testis, for example, displays no intrinsic circadian rhythmicity and the molecular mechanisms of clock gene activation in male germ cells appear to differ from other tissues. The study of the connecting routes that link the SCN to peripheral tissues is likely to reveal signalling pathways of fundamental physiological significance.