Paul H. Taghert, Ph.D.

Professor
Neuroscience

Neurosciences Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-3641

  • 314-362-3645

  • 314 660-1527

  • 314-362-3446

  • 8108

  • 469 McDonnell Medical Sciences Building

  • taghertp@pcg.wustl.edu

  • http://neurosci.wustl.edu/people/faculty/paul-taghert

  • circadian rhythms, Drosophila, neurobiology, neuropeptide, GPCR, 2nd messenger signaling

  • Circadian physiology and behavior

Research Abstract:

My laboratory studies two major questions in circadian neurobiology using the model system Drosophila.

First, we ask how circadian timing information is organized in neuronal circuits to regulate daily behavior. In Drosophila, a small (150) complement of neuronal pacemakers in the fly brain have special dedication to circadian timekeeping and control daily rhythmic locomotor behavior. Using novel imaging methods in collaboration with Tim Holy (Neuroscience, WUMS) to measure calcium levels brain-wide in vivo over 24 hr, we found that different circadian pacemaker groups are sequentially active at precise times of day. These represent different temporal outputs of the circadian pacemaker circuit, presumably controlling different physiological functions, (e.g., sensory, motor, integrative functions). Thus the circadian timing circuit of the fly brain produces multiple timing cues across the 24 hr cycle: we aim to define the respective downstream circuits controlled by these different circadian output elements and to define the endpoints they gate.

The sequential activation pattern is unexpected because these dynamic calcium oscillations depend on the circadian molecular clock within each pacemaker which runs synchronously across the network. Thus the second area we study is the cellular and molecular basis for decoding synchronous circadian timing system into staggered neuronal activation patterns. Predominantly, the transformation results from a series of suppressive signals within the network, representing numerous cell interactions mediated by neuropeptides. Morning appears to be the cardinal phase for neuronal activation, and all pacemaker groups except the canonical “Morning Pacemakers” are delayed by many hours via neuropeptide-mediated suppression of their calcium levels. The novel, long-lasting and pervasive nature of these suppressive signals prompt us to study the signaling details by which neuropeptides (like PDF) regulate calcium levels. We have shown that activation of the receptor for PDF (a GPCR) generates cAMP via certain adenylate cyclases, and that receptivity to PDF is itself daily 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.

Selected Publications:

Liang, X.. Holy T.E. & Taghert, P.H. (2017) A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs. Neuron. In press.

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. (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

Shafer, 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: 5/4/2017 9:50:10 AM

Imaging the fly brain in vivo in realtime
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