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Dissecting differential gene expression within the circadian neuronal circuit of Drosophila

Abstract

Behavioral circadian rhythms are controlled by a neuronal circuit consisting of diverse neuronal subgroups. To understand the molecular mechanisms underlying the roles of neuronal subgroups within the Drosophila circadian circuit, we used cell-type specific gene-expression profiling and identified a large number of genes specifically expressed in all clock neurons or in two important subgroups. Moreover, we identified and characterized two circadian genes, which are expressed specifically in subsets of clock cells and affect different aspects of rhythms. The transcription factor Fer2 is expressed in ventral lateral neurons; it is required for the specification of lateral neurons and therefore their ability to drive locomotor rhythms. The Drosophila melanogaster homolog of the vertebrate circadian gene nocturnin is expressed in a subset of dorsal neurons and mediates the circadian light response. The approach should also enable the molecular dissection of many different Drosophila neuronal circuits.

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Figure 1: Gene expression profiling of clock cells in the Drosophila brain.
Figure 2: mRNAs enriched in the subclasses of circadian neurons.
Figure 3: Functional classifications of the mRNAs enriched in the clock neurons.
Figure 4: Fer2 expression is required for behavioral circadian rhythms.
Figure 5: The Fer2 gene is required for the specification of the lateral neurons.
Figure 6: nocturnin-RD is rhythmically expressed in a subset of clock neurons.
Figure 7: NOCTURNIN mediates light-mediated behavioral response in dorsal neurons.

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Acknowledgements

We thank P. Hardin (Texas A&M University) for antisera to CLK as well as the Bloomington Stock Center, National Institute of Genetics of Japan (NIG) and Vienna Drosophila RNAi Center (VDRC) for fly stocks. We are grateful to J. Menet, W. Luo, K. Abruzzi, S. Bradley, L. Griffith, P. Garrity, S. Waddell, R. Allada, Y. Shang, P. Emery and J. Blau for comments on the manuscript. Y. Shang also provided the protocol for culture media preparation, and N. Francis helped with brain dissections. Some of this work was supported by a fellowship to E.N. from the Charles A. King Trust.

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Authors

Contributions

E.N. and M.R. conceived the idea of this project and wrote the manuscript; E.N. conducted molecular and behavioral experiments; K.S. conducted the microarray data analysis; E.K. performed the expression profiling of the adult neurons; K.S. and S.N. contributed to the development of the protocol for the Drosophila cell type–specific expression profiling; E.O. and T.T. generated a NOC-RD specific antibody.

Corresponding author

Correspondence to Michael Rosbash.

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Nagoshi, E., Sugino, K., Kula, E. et al. Dissecting differential gene expression within the circadian neuronal circuit of Drosophila. Nat Neurosci 13, 60–68 (2010). https://doi.org/10.1038/nn.2451

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