Paul H. Taghert (born January 13, 1953) is an American chronobiologist known for pioneering research on the roles and regulation of neuropeptide signaling in the brain using Drosophila melanogaster as a model.[1] He is a professor of neuroscience in the Department of Neuroscience at Washington University in St. Louis.[2]

Paul H. Taghert
BornJanuary 13, 1953 (1953-01-13) (age 71)
Alexandria, Egypt
NationalityEgyptian
American
Alma materReed College
University of Washington
Scientific career
FieldsNeurobiology
Chronobiology
InstitutionsWashington University in St. Louis

Background

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Taghert was born on January 13, 1953, in Alexandria, Egypt and grew up in Montclair, New Jersey. He attended Reed College from 1971 to 1975 and went on to pursue a PhD in zoology at the University of Washington in Seattle with Jim Truman. He did a postdoc under Corey Goodman at Stanford University from 1981 to 1984. As of 2016, he is a professor of neuroscience at Washington University in St. Louis and the Lab Head at the Taghert Lab at Washington University School of Medicine.[2][1]

Research contributions

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Studies of PDF/PDFR in Drosophila melanogaster

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Taghert and colleagues have identified the ~150 circadian clock neurons in the adult Drosophila melanogaster brain.[3] Two distinct regions, the small and large ventral lateral neurons (LNv), express the neuropeptide pigment dispersing factor (PDF) and contribute to circadian locomotor activity rhythms.[4] Taghert's group has made several contributions including the identification of mutants for the PDF neuropeptide gene - this revealed a specific behavioral syndrome indicating important contributions by this neuropeptide to normal circadian control of locomotor activity.[3] This was the first genetic study identifying secreted substances (and not just clock elements) as critical proteins for circadian neurophysiology.[4] This led the way to many studies by many laboratories that now evaluate how neuronal properties interweave and interact with cell intrinsic clock properties.[4]

Taghert's work involves employing the GAL4 activation and GAL80 inhibition of PDF to study PDF's necessity as a circadian pacemaker.[4] Experiments with the LNvs found that ablation of PDF via GAL80 inhibition only affected some aspects of behavioral rhythms, suggesting the presence of other regulators controlling circadian behavior.[4] To further examine the peptidergic pathways regulating PDF, Taghert and his group discovered the PDF receptor (PDFR), a class B1 G protein coupled receptor. Null mutations of PDFR suggests that it is also required for circadian rhythms in Drosophila melanogaster.[5]

Studies of PER and CRY in Drosophila melanogaster

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The Taghert group also demonstrated that PDF signaling influences pacemaker cell synchronicity through PER regulation, identified the PDF receptor, and identified critical PDF receptor signaling components.[6] They have shown that PDF receptor signals differently in different pacemaker groups, and that PDF receptor signaling interact with signals from Cryptochrome (CRY) to help sustain clock rhythmicity.[7]

Studies of DIMM in Drosophila melanogaster

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Taghert's work on DIMM addresses the genetic programs underlying neuron diversification.[8] Through a developmental studies approach, his work explores how peptidergic neurons in Drosophila use transcriptional control mechanisms to acquire properties like the selection of a unique neuropeptide phenotype.[9] The bHLH protein DIMM is an example of a transcriptional control mechanism that operates in neurosecretory neurons and is responsible for the cells’ ability to accumulate, process, and package large amounts of secretory peptides.[8]

DIMM confers a specific peptidergic phenotype to neurons, referred to as LEAP cells (Large cells that Episodically release Amidated Peptides).[9] To map DIMM expression in Drosophila peptidergic systems, a large panel of peptide antibodies and gene reporters were used.[8] It was found that there is a substantial correlation of DIMM expression with peptidergic phenotypes. At a molecular level, DIMM concerns secretory peptides that are amidated, and at a cellular level, DIMM concerns peptidergic neurons which are neurosecretory.[9] Current research involves molecular pathways by which DIMM levels are induced in response to environmental challenges.[2]

Notable publications

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  • Renn, S.C.P.; J.H., Park; Rosbash, M.; Hall, J.C.; Taghert, P.H. (1999). "A pdfNeuropeptide Gene Mutation and Ablation of PDF Neurons Each Cause Severe Abnormalities of Behavioral Circadian Rhythms in Drosophila". Science. 99 (7): 781–802. doi:10.1016/S0092-8674(00)81676-1. PMID 10619432.
  • Mertens, Inge; Vandingenen, Anick; Johnson, Eric C.; Shafer, Orie; Li, W.; Trigg, J.S.; De Loof, Arnold; Schoofs, Liliane; Taghert, Paul (2005). "PDF Receptor Signaling in Drosophila Contributes to Both Circadian and Biotactic Behaviors". Neuron. 48 (2): 213–219. doi:10.1016/j.neuron.2005.09.009. PMID 16242402.

References

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  1. ^ a b Panda, Satchidananda; Antoch, Marina P.; Miller, Brooke H.; Su, Andrew I.; Schook, Andrew B.; Straume, Marty; Schultz, Peter G.; Kay, Steve A.; Takahashi, Joseph S.; Hogenesch, John B. (2002). "Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock". Cell. 109 (3): 307–320. doi:10.1016/S0092-8674(02)00722-5. PMID 12015981.
  2. ^ a b c "Paul Taghert". Washington University in St. Louis Division of Biology & Biomedical Sciences.
  3. ^ a b Peschel, Nicolai (May 20, 2011). "Setting the clock – by nature: Circadian rhythm in the fruitfly Drosophila melanogaster". FEBS Letters. 585 (10): 1435–1442. doi:10.1016/j.febslet.2011.02.028. PMID 21354415.
  4. ^ a b c d e Stoleru, Dan; Peng, Ying; Agosto, José; Rosbash, Michael (14 October 2004). "Coupled oscillators control morning and evening locomotor behavior of Drosophila". Nature. 431 (7010): 862–868. Bibcode:2004Natur.431..862S. doi:10.1038/nature02926. PMID 15483615. S2CID 4394441.
  5. ^ Kunst, Michael; Tso, Matthew C.F.; Ghosh, D. Dipon; Herzog, Erik D.; Nitabach, Michael N. (5 November 2014). "Rhythmic control of activity and sleep by class B1 GPCRs". Critical Reviews in Biochemistry and Molecular Biology. 50 (1): 18–30. doi:10.3109/10409238.2014.985815. PMC 4648372. PMID 25410535.
  6. ^ Herzog, Erik D. (October 2007). "Neurons and networks in daily rhythms". Nature Reviews Neuroscience. 8 (10): 790–802. doi:10.1038/nrn2215. PMID 17882255. S2CID 33687097.
  7. ^ Li, Yue; Guo, Fang; Shen, James; Rosbash, Michael (February 11, 2014). "PDF and cAMP enhance PER stability in Drosophila clock neurons". Proceedings of the National Academy of Sciences of the United States of America. 111 (13): E1284–E1290. Bibcode:2014PNAS..111E1284L. doi:10.1073/pnas.1402562111. PMC 3977231. PMID 24707054.
  8. ^ a b c Dongkook, Park; Veenstra, Jan; Park, Jae; Taghert, Paul (March 26, 2008). "Mapping Peptidergic Cells in Drosophila: Where DIMM Fits In". PLOS ONE. 3 (3): e1896. Bibcode:2008PLoSO...3.1896P. doi:10.1371/journal.pone.0001896. PMC 2266995. PMID 18365028.
  9. ^ a b c Nassel, Dick R. (September 2010). "Drosophila neuropeptides in regulation of physiology and behavior". Progress in Neurobiology. 92 (1): 42–104. doi:10.1016/j.pneurobio.2010.04.010. PMID 20447440. S2CID 24350305.
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