Abstract
Epidermal growth factor receptor (EGFR) signaling in the mammalian hypothalamus is important in the circadian regulation of activity. We have examined the role of this pathway in the regulation of sleep in Drosophila melanogaster. Our results demonstrate that rhomboid (Rho)- and Star-mediated activation of EGFR and ERK signaling increases sleep in a dose-dependent manner, and that blockade of rhomboid (rho) expression in the nervous system decreases sleep. The requirement of rho for sleep localized to the pars intercerebralis, a part of the fly brain that is developmentally and functionally analogous to the hypothalamus in vertebrates. These results suggest that sleep and its regulation by EGFR signaling may be ancestral to insects and mammals.
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Acknowledgements
We dedicate this paper to the memory of our mentor, colleague and friend, John Newport, who died 25 December 2005. We thank A. Guichard for essential technical guidance and advice, E. J. Kim and J. Wagner for technical assistance, M. Kaneko, R. Andretic, H. Dierick, P. Shaw, C.P. Kyriacou, E. Green, T. Roenneberg and M. Merrow for assistance with data analysis, and E. Bier, J. Wang, W. McGinnis, R. Andretic, M. Kaneko and H. Dierick for comments on the manuscript. This work was supported by a US National Institutes of Health grant (J.W.N.) and a US National Science Foundation grant No. 0432063 (R.J.G.). R.J.G. is the Dorothy and Lewis B. Cullman Fellow at the Neurosciences Institute, which is supported by the Neurosciences Research Foundation.
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Foltenyi, K., Greenspan, R. & Newport, J. Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila. Nat Neurosci 10, 1160–1167 (2007). https://doi.org/10.1038/nn1957
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DOI: https://doi.org/10.1038/nn1957