Strict control of when cells divide is vital to guarantee normal growth and to avoid tumour formation. Therefore, understanding the timing mechanisms in normal cells is of great medical importance. Remarkably, cells from bacteria to man often divide only at certain times of day. Also many other aspects of metabolism and behaviour occur at certain periods of the day, reflecting their control by internal biological clocks. A central pacemaker structure in the brain controls rhythms of behaviour and hormone release.
However, so-called “peripheral†biological clocks are present in every cell, where they regulate the daily changes in cell metabolism. Key steps of the cell division process also appear to be subjected to this cell clock regulation. Very little is known to date how the two clock systems interact. By examining zebrafish strains with defects in hormone production, we have revealed that the steroid hormone cortisol is essential for cell clocks to generate daily rhythms of cell proliferation. Interestingly, this does not require the circadian changes in cortisol levels observed in normal zebrafish: Treating the cortisol defective strains with a constant level of a drug mimicking cortisol effects results in normal circadian cell division rhythms. Our work shows how internal cell timers can cooperate with hormonal signals to regulate at what time cells divide.Â
