Cellular circadian clocks in the pineal.

Daily rhythms are a fundamental feature of all living organisms; most are synchronized by the 24 hr light/dark (LD) cycle. In most species, these rhythms are generated by a circadian system, and free run under constant conditions with a period close to 24 hr. To function properly the system needs a pacemaker or clock, an entrainment pathway to the clock, and one or more output signals. In vertebrates, the pineal hormone melatonin is one of these signals which functions as an internal time-keeping molecule. Its production is high at night and low during day. Evidence indicates that each melatonin producing cell of the pineal constitutes a circadian system per se in non-mammalian vertebrates. In addition to the melatonin generating system, they contain the clock as well as the photoreceptive unit. This is despite the fact that these cells have been profoundly modified from fish to birds. Modifications include a regression of the photoreceptive capacities, and of the ability to transmit a nervous message to the brain. The ultimate stage of this evolutionary process leads to the definitive loss of both the direct photosensitivity and the clock, as observed in the pineal of mammals. This review focuses on the functional properties of the cellular circadian clocks of non-mammalian vertebrates. How functions the clock? How is the photoreceptive unit linked to it and how is the clock linked to its output signal? These questions are addressed in light of past and recent data obtained in vertebrates, as well as invertebrates and unicellulars.