The Development and Decay of the Circadian Clock in Drosophila melanogaster

Abstract

The way in which the circadian clock mechanism develops and decays throughout life is interesting for a number of reasons and may give us insight into the process of aging itself. The Drosophila model has been proven invaluable for the study of the circadian clock and development and aging. Here we review the evidence for how the Drosophila clock develops and changes throughout life, and present a new conceptual model based on the results of our recent work. Firefly luciferase lines faithfully report the output of known clock genes at the central clock level in the brain and peripherally throughout the whole body. Our results show that the clock is functioning in embryogenesis far earlier than previously thought. This central clock in the fly remains robust throughout the life of the animal and only degrades immediately prior to death. However, at the peripheral (non-central oscillator level) the clock shows weakened output as the animal ages, suggesting the possibility of the breakdown in the cohesion of the circadian network.

Keywords: aging; central and peripheral clocks; clock gene reporter.

Figure 1

Life stages of Drosophila and recent findings on clock development from the embryo to eclosion as an adult. The diagram shows the negative correlation between temperature and development as defined in [34]. Higher temperature speeds up development and lower temperature slows it down within a range of 16 °C to 29 °C [35]. At 16 °C, the embryonic stage is prolonged by approximately twice the developmental time compared to 25 °C [36]. Based on our findings from a development study in Drosophila, circadian clock gene expression in the central clock neurons and their light-sensitivity start in the embryonic stage, which is earlier than previously thought. Clock gene expression in the peripheral clocks begin in embryos but only oscillate in synchrony in adults, when light-sensitivity is present [32]. The synchronized peripheral oscillations and light response at the whole body level in Drosophila occur after eclosion. We infer that period is expressed within different peripheral clocks around the body, which could be cyclic [37] or non-cyclic, but not synchronized at the whole animal level before eclosion. Our results also suggest that photoreceptors in peripheral clocks have not fully developed before the adult stage because PER expression is not synchronized in light-dark (LD) cycles. This is supported by a recent finding that, although expression of cryptochrome exists in certain larval peripheral tissue but not others, it lacks the function that mediates light-entrainment in both central and peripheral clocks in adult Drosophila [38].

Figure 2

Conceptual model of the development and changes in the clock over the lifetime of Drosophila. (A) Summary in longitudinal format and (B) specific changes characterizing the function of the clock at each life stage [43,48].