Abstract: The circadian system consists of a multiple oscillators in the brain and the body that drive rhythms of behavior and physiology. Although we have some understanding of the molecular clock located in these organs/tissues, little is known about mechanisms that transmit time-of-day signals from the clock to produce overt rhythms or those that synchronize clocks across the organism.
Using a Drosophila model, we identified an important role for peptidergic signaling in both processes. The central clock cells in Drosophila are well known to release a neuropeptide, Pigment Dispersing Factor (PDF), which couples neurons within the brain clock network and is required for robust behavioral rhythms. We recently found that transmission of circadian signals for rest:activity rhythms also requires peptides within the pars intercerebralis (PI), the fly equivalent of the hypothalamus. We showed that the PI is important for the circadian output of rest:activity and two groups of cells within the PI are particularly relevant, those that secrete the peptides DH44 and SIFamide respectively. In recent work we have identified a role for yet other peptide in the brain control of peripheral circadian gene expression. We find that at least one of these peptides has a similar function in mammals.
1. "Identification of a Circadian Output Circuit for Rest: Activity Rhythms in Drosophila," Cell, 2014.
2. "Regulation of Circadian Behavioral Output via a MicroRNA-JAK/STAT Circuit," Cell, 2012.
3. "The Circadian Clock Interacts with Metabolic Physiology to Influence Reproductive Fitness," Cell Metabolism, 2011.