Reevaluation of Drosophila Melanogaster's Neuronal Circadian Pacemakers Reveals New Neuronal Classes

Overview

Journal J Comp Neurol

Specialty Neurology

Date 2006 Jul 21

PMID 16856134

Citations 101

Authors

Orie Thomas Shafer

Charlotte Helfrich-Forster

Susan Christine Portia Renn

Paul H Taghert

Affiliations

Soon will be listed here.

Abstract

In the brain of the fly Drosophila melanogaster, approximately 150 clock-neurons are organized to synchronize and maintain behavioral rhythms, but the physiological and neurochemical bases of their interactions are largely unknown. Here we reevaluate the cellular properties of these pacemakers by application of a novel genetic reporter and several phenotypic markers. First, we describe an enhancer trap marker called R32 that specifically reveals several previously undescribed aspects of the fly's central neuronal pacemakers. We find evidence for a previously unappreciated class of neuronal pacemakers, the lateral posterior neurons (LPNs), and establish anatomical, molecular, and developmental criteria to establish a subclass within the dorsal neuron 1 (DN1) group of pacemakers. Furthermore, we show that the neuropeptide IPNamide is specifically expressed by this DN1 subclass. These observations implicate IPNamide as a second candidate circadian transmitter in the Drosophila brain. Finally, we present molecular and anatomical evidence for unrecognized phenotypic diversity within each of four established classes of clock neurons.

Citing Articles

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References

Samson M, Lisbin M, White K . Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon. Genetics. 1995; 141(3):1101-11. PMC: 1206833. DOI: 10.1093/genetics/141.3.1101. View

Ewer J, Frisch B, Rosbash M, Hall J . Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms. J Neurosci. 1992; 12(9):3321-49. PMC: 6575742. View

Helfrich-Forster C, Winter C, Hofbauer A, Hall J, Stanewsky R . The circadian clock of fruit flies is blind after elimination of all known photoreceptors. Neuron. 2001; 30(1):249-61. DOI: 10.1016/s0896-6273(01)00277-x. View

Cyran S, Buchsbaum A, Reddy K, Lin M, Glossop N, Hardin P . vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell. 2003; 112(3):329-41. DOI: 10.1016/s0092-8674(03)00074-6. View

Schoning J, Staiger D . At the pulse of time: protein interactions determine the pace of circadian clocks. FEBS Lett. 2005; 579(15):3246-52. DOI: 10.1016/j.febslet.2005.03.028. View

Nitabach M, Blau J, Holmes T . Electrical silencing of Drosophila pacemaker neurons stops the free-running circadian clock. Cell. 2002; 109(4):485-95. DOI: 10.1016/s0092-8674(02)00737-7. View

Stoleru D, Peng Y, Agosto J, Rosbash M . Coupled oscillators control morning and evening locomotor behaviour of Drosophila. Nature. 2004; 431(7010):862-8. DOI: 10.1038/nature02926. View

Helfrich-Forster C . Robust circadian rhythmicity of Drosophila melanogaster requires the presence of lateral neurons: a brain-behavioral study of disconnected mutants. J Comp Physiol A. 1998; 182(4):435-53. DOI: 10.1007/s003590050192. View

Grima B, Chelot E, Xia R, Rouyer F . Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain. Nature. 2004; 431(7010):869-73. DOI: 10.1038/nature02935. View

10.

Helfrich-Forster C . The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster. Microsc Res Tech. 2003; 62(2):94-102. DOI: 10.1002/jemt.10357. View

11.

Baggerman G, Cerstiaens A, De Loof A, Schoofs L . Peptidomics of the larval Drosophila melanogaster central nervous system. J Biol Chem. 2002; 277(43):40368-74. DOI: 10.1074/jbc.M206257200. View

12.

Helfrich-Forster C . Techniques that revealed the network of the circadian clock of Drosophila. Methods Enzymol. 2005; 393:439-51. DOI: 10.1016/S0076-6879(05)93021-8. View

13.

Shafer O, Rosbash M, Truman J . Sequential nuclear accumulation of the clock proteins period and timeless in the pacemaker neurons of Drosophila melanogaster. J Neurosci. 2002; 22(14):5946-54. PMC: 6757919. DOI: 20026628. View

14.

ONeill E, Rebay I, Tjian R, Rubin G . The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell. 1994; 78(1):137-47. DOI: 10.1016/0092-8674(94)90580-0. View

15.

Liu X, Zwiebel L, Hinton D, Benzer S, Hall J, Rosbash M . The period gene encodes a predominantly nuclear protein in adult Drosophila. J Neurosci. 1992; 12(7):2735-44. PMC: 6575836. View

16.

Taghert P, Hewes R, Park J, OBrien M, Han M, Peck M . Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila. J Neurosci. 2001; 21(17):6673-86. PMC: 6763108. View

17.

Hardin P . Transcription regulation within the circadian clock: the E-box and beyond. J Biol Rhythms. 2004; 19(5):348-60. DOI: 10.1177/0748730404268052. View

18.

Verleyen P, Baggerman G, Wiehart U, Schoeters E, Van Lommel A, De Loof A . Expression of a novel neuropeptide, NVGTLARDFQLPIPNamide, in the larval and adult brain of Drosophila melanogaster. J Neurochem. 2003; 88(2):311-9. DOI: 10.1046/j.1471-4159.2003.02161.x. View

19.

Moses K, ELLIS M, Rubin G . The glass gene encodes a zinc-finger protein required by Drosophila photoreceptor cells. Nature. 1989; 340(6234):531-6. DOI: 10.1038/340531a0. View

20.

Dunlap J . Molecular bases for circadian clocks. Cell. 1999; 96(2):271-90. DOI: 10.1016/s0092-8674(00)80566-8. View