Biological clocks and the digestive system.

Circadian rhythms play a major role in regulating the digestive systems of many organisms. Cell proliferation, migration, differentiation, and even structure vary as a function of time of day in many different digestive organs (i.e., stomach, gut, liver, and pancreas) and cell types, resulting in regionally specific temporal variations in protein and gene expression. Feeding and light set the hands of the digestive clock(s). However, the clockwork has a genetic basis. During the last 10 years, new developments have emerged in our understanding of how cells keep time. Surprisingly, clock genes in mammals are expressed not only in specialized time keepers in the brain, but also in peripheral organs, suggesting that the ability to keep time may also belong to cells within the digestive system. This article reviews several classic examples of circadian variation in the digestive system, with an emphasis on rhythms in cell proliferation, function, and structure. It also briefly summarizes several new ideas about how cells in the brain and possibly the digestive system keep time.