The Drosophila period gene (per) is a likely component of a circadian pacemaker. per protein (PER) participates in the regulation of its own expression, at least in part at the transcriptional level. There is at present no direct evidence that the effect of PER on its own transcription is intracellular. Results presented in this paper show that (i) the circadian oscillations of both per mRNA and PER protein are quantitatively similar in eye photoreceptor cells and in brain; (ii) constitutive overexpression of PER only in photoreceptors R1‐R6 represses endogenous per RNA cycling in these cells but not in other per‐expressing cells; (iii) the overexpression construct has no effect on locomotor activity rhythms. These results indicate that the autoregulation of per expression is a direct, intracellular event and suggest that each per‐expressing cell contains an autonomous oscillator of which the per feedback loop is a component.

The period (per) gene is thought to be part of the Drosophila circadian pacemaker. The circadian fluctuations in per RNA and protein that constitute theper feedback loop appear to be required for pacemaker function, and have been measured in head neuronal tissues that are necessary for locomotor activity and eclosion rhythms. The per gene is also expressed in a number of neuronal and nonneuronal body tissues for which no known circadian phenomena have been described. To determine whether per might affect some circadian function in these body tissues, per RNA cycling was examined. These studies show that per RNA cycles in the same phase and amplitude in head and body tissues during light-dark cycles. One exception to this is the lack ofper RNA cycling in the ovary, which also appears to be the only tissue in which PER protein is primarily cytoplasmic.In constant darkness, however, the amplitude ofper RNA cycling dampens much more quickly in bodies than in heads. Taken together, these results indicate that circadian oscillators are present in head and body tissues in which PER protein is nuclear and that these oscillators behave differently.Circadian rhythms influence many biochemical, physiological, and behavioral processes in plant, animal, and microbial systems (10). In any organism, different rhythms must be coordinated with respect to each other and to the time of day. This coordination results from the action of an endogenous, genetically driven circadian clock that persists under constant environmental conditions, is reset by environmental parameters such as light and temperature, and is relatively temperature independent.To understand the molecular circuitry underlying circadianclock function, genetic screens have been performed to isolate mutants having altered circadian rhythms. Mutations in the period (per) gene of the fruit fly Drosophila melanogaster can shorten (perS), lengthen (perL), or abolish (perel) circadian rhythms in eclosion and locomotor activity (17). As per function also appears to be necessary for entrainment (to light-dark cycles) of the circadian clock (7), it is likely that per expression is required for flies to either measure or tell time. An important aspect of per expression is that its mRNA and protein products undergo daily fluctuations in abundance (12, 36). These fluctuations constitute a feedback loop in which per mRNA is the template for per protein (PER) synthesis and PER is necessary for the circadian synthesis of its own mRNA (12,36). Since PER is nuclear in most tissues (22) and is able to repress its own RNA's synthesis (35), it is thought to function by directly repressing its own gene's activity (13). The regulatory features of the per feedback loop parallel formal theoretical models of self-sustaining circadian oscillators and might also accommodate the effects of PER on circadian behavior (13). Thus, the per feedback loop is thought to be a critical component of the Drosophila circadian clock.The per feedback loop was initially shown to function in many neuronal ti...

Circadian fluctuations in per mRNA and protein are central to the operation of a negative feedback loop that is necessary for setting the free-running period and for entraining the circadian oscillator to light-dark cycles. In this study, per mRNA cycling and locomotor activity rhythms were measured under different light and dark cycling regimes to determine how photoperiods affect the molecular feedback loop and circadian behavior, respectively. These experiments reveal that per mRNA peaks in abundance 4 h after lights-off in photoperiods of <16 h, that phase shifts in per mRNA cycling and behavioral rhythmicity occur rapidly after flies are transferred from one photoperiod to another, and that photoperiods longer than 20 h abolish locomotor activity rhythms and leave per mRNA at a median constitutive level. These results indicate that the per feedback loop uses lights-off as a phase reference point and suggest (along with previous findings for per 01 and tim 01 ) that per mRNA cycling is not regulated via simple negative feedback from the per protein.Circadian rhythms in biochemical, physiological, and behavioral phenomena are a fundamental adaptation of both prokaryotic and eukaryotic organisms to environmental changes that occur over a 24-h period. These rhythms are driven by an endogenous clock that continues to operate under constant environmental conditions. The timekeeping component of the clock, or pacemaker, maintains a periodicity that can be hours longer or shorter than 24 h, and it is synchronized to local time by such environmental signals as light and dark. A stable phase relationship between the pacemaker and its Zeitgeber is clearly a prerequisite if preprogrammed biological changes are to be appropriately timed to daily environmental changes. Physiological and behavioral experiments have been used to determine how the clock adjusts its phase to circadian cycles composed of different proportions of light and dark. During these different photoperiodic conditions, the phase of the circadian pacemaker (and its physiological and behavioral output) is altered so that a stable phase relationship is maintained (26). Because of the lack of measurable pacemaker components, however, these physiological studies could not address the molecular mechanism by which the clock adjusts its phase to accommodate different environmental light-dark (LD) cycles.Genetic screens for rhythm mutants have been used to identify components of the circadian pacemaker. Mutations in the per gene from Drosophila melanogaster can shorten (per S and per) circadian rhythms of locomotor activity and eclosion during constant dark (DD) conditions (16,17) and alter the phase of locomotor activity and eclosion rhythms during LD cycling conditions (3,10,11,17,30). These behavioral effects of the per mutants are paralleled at the molecular level by circadian fluctuations in the abundance of per mRNA and per protein (PER) (12, 41). These fluctuations in per mRNA and protein levels compose a negative feedback loop in which per mRNA serves ...