We are interested in signaling mechanisms used by circadian pacemaker neurons to organize daily locomotor behavior. There has been tremendous progress in recent years in defining the molecular basis of the cell autonomous clockwork mechanism that underlies circadian timekeeping. That definition has permitted the identification of the primary circadian clock neurons within the brain. In turn, that has presented the opportunity to re-examine fundamental issues concerning the neural basis of behavior. This research program features cellular, molecular and genetic techniques to understand how signals are passed from the primary pacemakers to responsive neurons. Previously we showed that the neuropeptide PDF is the principal circadian transmitter in Drosophila. Genetic evidence indicates it is the most important signal used by the primary clock cells (the LN-v neurons). We will extend that information by performing experiments that are designed to ask where and when PDF signals circadian time within the brain. Further, we will identify and characterize the receptor(s) for PDF. Definition of the PDF receptor will permit a description of which neural elements and which circuits respond to the circadian transmitter. We can also begin to ask what are the long-term consequences (signal transduction pathways) that are modulated as a result of PDF receptor activation. Because circadian signaling occurs on such a long time base (many hours), we hypothesize that PDF signaling may include transcriptional regulation. We have identified several genes whose expression levels are pdf-dependent and which cycle on a daily basis. We propose now to demonstrate their role as PDF targets for the mediation of circadian signaling. Finally, we have performed an extensive genome-wide microarray screen for circadian gene expression in the Drosophila head. We have identified 22 circadian genes, of which 15 are novel in the context of circadian biology. We hypothesize that most of these circadian genes participate in circadian output mechanisms, and propose experiments to address this possibility ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Brady, Linda S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Anatomy/Cell Biology
Schools of Medicine
Saint Louis
United States
Zip Code
Liang, Xitong; Holy, Timothy E; Taghert, Paul H (2017) A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs. Neuron 94:1173-1189.e4
Diao, Feici; Mena, Wilson; Shi, Jonathan et al. (2016) The Splice Isoforms of the Drosophila Ecdysis Triggering Hormone Receptor Have Developmentally Distinct Roles. Genetics 202:175-89
Liang, Xitong; Holy, Timothy E; Taghert, Paul H (2016) Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²? rhythms in vivo. Science 351:976-81
Klose, Markus; Duvall, Laura; Li, Weihua et al. (2016) Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation. Neuron 90:781-794
Langenhan, Tobias; Barr, Maureen M; Bruchas, Michael R et al. (2015) Model Organisms in G Protein-Coupled Receptor Research. Mol Pharmacol 88:596-603
Duvall, Laura B; Taghert, Paul H (2013) E and M circadian pacemaker neurons use different PDF receptor signalosome components in drosophila. J Biol Rhythms 28:239-48
Duvall, Laura B; Taghert, Paul H (2012) The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila. PLoS Biol 10:e1001337
Taghert, Paul H; Nitabach, Michael N (2012) Peptide neuromodulation in invertebrate model systems. Neuron 76:82-97
Im, Seol Hee; Li, Weihua; Taghert, Paul H (2011) PDFR and CRY signaling converge in a subset of clock neurons to modulate the amplitude and phase of circadian behavior in Drosophila. PLoS One 6:e18974
Duvall, Laura B; Taghert, Paul H (2011) Circadian rhythms: biological clocks work in phospho-time. Curr Biol 21:R305-7

Showing the most recent 10 out of 24 publications