Peripheral clocks and their role in circadian timing: insights from insects

Abstract

Impressive advances have been made recently in our understanding of the molecular basis of the cell–autonomous circadian feedback loop; however, much less is known about the overall organization of the circadian systems. How many clocks tick in a multicellular animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock–containing tissues were based on the analysis of behavioural rhythms and identified brain–located timing centres in a variety of animals. Characterization of several essential clock genes and analysis of their expression patterns revealed that molecular components of the clock are active not only in the brain, but also in many peripheral organs ofDrosophilaand other insects as well as in vertebrates. Subsequent experiments have shown that isolated peripheral organs can maintain self–sustained and light sensitive cycling of clock genesin vitro. This, together with earlier demonstrations that physiological output rhythms persist in isolated organs and tissues, provide strong evidence for the existence of functionally autonomous local circadian clocks in insects and other animals. Circadian systems in complex animals may include many peripheral clocks with tissue–specific functions and a varying degree of autonomy, which seems to be correlated with their sensitivity to external entraining signals.