Role of molecular oscillations in generating behavioral rhythms in Drosophila.

Circadian oscillations of clock gene products are thought to provide time-of-day signals that drive overt rhythms. In Drosophila, RNA and protein levels of the period and timeless genes oscillate and the proteins autoregulate their transcription. To test the relevance of these oscillations, we expressed period and timeless under control of constitutively active promoters. Constitutive expression of either RNA supported protein cycling and behavioral rhythms in the respective null mutant, although constitutive timeless was less effective than constitutive period. Constitutive expression of both genes restored behavioral rhythms that showed deficits in photic resetting and drove cyclic expression of the clock-controlled RNA, vrille. Overexpression of either period or timeless, but especially timeless, attenuated behavioral rhythmicity and protein cycling in lateral neurons. We propose that the two proteins must cycle to drive rhythmic expression of downstream genes.