Clock genes in mammalian peripheral tissues

Abstract.

For many years, neurons of the suprachiasmatic nucleus (SCN) in the hypothalamus were thought to contain the unique mammalian clock controlling circadian rhythmicity of peripheral tissues via neural and humoral signals. Surprisingly, the cloning and characterisation of mammalian clock genes have revealed that they are expressed in a circadian manner throughout the body. It is generally accepted now that peripheral cells contain a circadian clock which is similar to the one present in SCN neurons, although only the latter seems to be self-sustained. It is still unclear how these peripheral clocks are synchronised by the central SCN clock, albeit humoral signals appear to be crucial. Interestingly, peripheral clocks can be uncoupled from the central clock in particular conditions such as restricted-feeding, allowing peripheral tissues to adapt themselves to cues incompatible to other cues perceived by the SCN (mainly the photoperiod). Whereas circadian clocks have been intensively dissected, little is known about the mechanisms by which these clocks regulate the expression of clock-controlled genes. Direct regulation for some of them by the products of clock genes was recently documented, but this probably represents the exception rather than the rule. We should soon be able to describe complete circadian transcriptional cascades from clock genes to enzymes and structural proteins. In addition to circadian humoral and neural signals, these cascades should help us to understand how gene expression, physiology and behaviour are influenced by the rotation of the Earth around its axis.