Teamwork is all very well but some intricate tasks, such as the performance of a symphony, need a leader to ensure that all participants start and stop at the right times. Now, new work shows that the symphonic complexities of circadian rhythmicity fall into this category, and, in this case, the transcriptional activator Clock (Clk) is the maestro waving the baton.

Circadian rhythms are amazingly widespread: they affect behaviour, physiology and gene expression in many different tissues, from Drosophila to human. In Drosophila, a complex series of interdependent feedback loops is involved in circadian gene expression. Clk has a role as both transcriptional activator and inhibitor in these loops, and might be the limiting factor for the crucial CLK/CYC heterodimer. This last role marked Clk as a potential 'master' circadian control gene.

In their recent study, published in Cell, J. Zhao and colleagues performed an ingenious test of this hypothesis. They focused their efforts on the fly brain, in which Clk-expressing cells are uncommon but vital for controlling the most prominent circadian rhythm in flies: the daily cycle of rest and activity.

The authors fused binding sites for the yeast transcription factor GAL4 upstream of Clk cDNA and, using a GAL4 driver, were sub sequently able to misexpress Clk in brain cells that did not normally express clock genes. Not only did this misexpression induce circadian gene expression of timeless ( tim ), a clock gene directly regulated by Clk, but also of cryptochrome ( cry ), a gene with a rhythmic expression pattern that is the inverse of that of tim and is normally repressed by Clk: clear evidence that Clk expression was sufficient to induce an ectopic circadian clock.

Transgenic flies in which misexpressed Clk induced an ectopic circadian clock had patterns of activity during light–dark cycles that were notably different from those of wild-type flies: instead of two peaks of activity in the morning and evening they had a single daytime peak. So, these data indicate that ectopic clocks generated by misexpressed Clk can directly affect circadian rhythms in behaviour.

Zhao et al. took this work one step further. They showed that another important clock gene, period ( per ), when ectopically expressed in the same way as Clk, could not induce rhythmic expression of tim. So, it seems that only Clk can induce an ectopic circadian clock.

The identification of Clk as a master controller in flies has widespread implications. The mammalian system that controls circadian rhythm is similar to that of Drosophila, so the mammalian Clk orthologue might be equally important.

Even more interesting is the similarity between this discovery and that of master genes that control development, such as eyeless ( ey ). Will most complex regulatory networks, including those that underlie complex behaviours, perhaps turn out to have 'conductors' that are sufficient to initiate and organize the performance of the whole programme?