PDP1ε Functions Downstream of the Circadian Oscillator to Mediate Behavioral Rhythms

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Abstract
TheDrosophilacircadian oscillator is composed of autoregulatoryperiod/timeless(per/tim) andClock(Clk) feedback loops that control rhythmic transcription. In theClkloop, CLOCK-CYCLE heterodimers activatevrille(vri) andPAR domain protein 1ε (Pdp1ε) transcription, then sequential repression by VRI and activation by PDP1ε mediate rhythms inClktranscription. Because VRI and PDP1ε bind the same regulatory element, the VRI/PDP1ε ratio is thought to control the level ofClktranscription. Thus, constant high or low PDP1ε levels in clock cells should eliminateClkmRNA cycling and disrupt circadian oscillator function. Here we show that reducing PDP1ε levels in clock cells by ∼70% via RNA interference or increasing PDP1ε levels by ∼10-fold in clock cells does not alterClkmRNA cycling or circadian oscillator function. However, constant low or high PDP1ε levels in clock cells disrupt locomotor activity rhythms despite persistent circadian oscillator function in brain pacemaker neurons that extend morphologically normal projections into the dorsal brain. These results demonstrate that the VRI/PDP1ε ratio neither controlsClkmRNA cycling nor circadian oscillator function and argue that PDP1ε is not essential forClkactivation. PDP1ε is nevertheless required for behavioral rhythmicity, which suggests that it functions to regulate oscillator output.