Paul H. Taghert, Ph.D.
Developmental, Regenerative and Stem Cell Biology Program
My laboratory studies two major questions in circadian neurobiology using the model system Drosophila.
Firstly, we ask how circadian timing information is transmitted through neuronal circuits to regulate daily behavior. Here we describe normal in vivo activity patterns of the small (150) complement of neuronal pacemakers in the fly brain that control daily rhythmic locomotor behavior. Using novel imaging methods in collaboration with Tim Holy (Neuroscience, WUMS) to measure calcium levels in vivo over 24 hr, we found that different pacemaker groups are active at precise times of day. We also learned that the neuropeptide PDF secreted by morning oscillators delays the calcium phase in evening oscillators by many hours. Thus the circadian timing circuit of the fly brain produces multiple timing cues across the 24 hr cycle. These multi-phasic signals are generated in part by neuropeptide-mediated interactions between pacemakers.
Secondly, we ask about the molecular details of signaling downstream of PDF neuropeptide receptor in this circadian circuit. We have shown that activation of this GPCR generates cAMP via certain adenylate cyclases, and that receptivity to PDF is itself rhythmic, with a peak at dawn (which is when behaviorally-functional signaling takes place). Further the rhythm of sensitivity is gated by the small GTPase Ral A. Ultimately we would like to understand how this GPCR signals to control the phases of daily calcium peaks in different pacemaker neurons.
Klose, M., Duvall, L.B., Li, W., Liang, X., Ren, C., Steinbach, J.H., & Taghert, P.H. (2016) Functional Pdf Signaling In the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation. Neuron S0896-6273(16)30060-5. PMID: 27161526
Liang, X., Holy, T.E., & Taghert, P.H. (2016) Synchronous Drosophila circadian pacemakers display non-synchronous Ca2+ rhythms in vivo. Science (Wash.), 351: 976-981. PMID: 26917772
Duvall, L.B. & Taghert, P.H. (2013) E and M Pacemaker Neurons use different receptor signalosome components in Drosophila. J. Biol. Rhythms 28(4):239-48. PMID: 23929551
Duvall, L.B. & Taghert, P.H. (2012) The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila. PLoS Biology 10(6): e1001337. PMID: 22679392
Im, S.H. & Taghert, P.H. (2010) PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila. J Comp Neurol. 518(11):1925-45. PMID: 20394051
Share, O.T., Kim, D.J., Nikolaev, V., Dunbar-Jaffe, R., Lohse, M. & Taghert, P.H. (2008) Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging. Neuron 58: 223-237. PMID: 18439407
Martens, I., Vandingenen, A., Johnson, E.C., Shafer, O.T., Li, W., Trigg, J.S., De Loof, A., Schools, L. & Taghert, P.H. (2005) PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. Neuron 48: 213-219. PMID: 16242402
Lin, Y., Stormo, G.D., & Taghert, P.H. (2004) The neuropeptide pigment-dispersing factor coordinates pacemaker interactions in the Drosophila circadian system. J Neurosci. 24:7951-7. PMID: 15356209
Lin, Y., Han, M., Shimada, B., Wang, L., Gibler, T.M., Amaorone, A., Awad, T., Stormo, G.D., Van Gelder, R.N., & Taghert, P.H. (2002) Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proc. Nat. Acad. Sci, USA 99:9562-9567. PMID: 12089325
Renn, S.C.P., Park, J., Rosebash, M., Hall, J.C. & Taghert, P.H. (1999) A pdf neuropeptide gene mutation and ablation of PDF-containing neurons each cause severe abnormalities of circadian behavioral rhythms in Drosophila. Cell, 99:791-802. PMID: 10619432
Last Updated: 5/23/2016 9:10:42 AM
Imaging the fly brain in vivo in realtime