Ecdysone acts through cortex glia to regulate sleep in Drosophila
- Howard Hughes Medical Institute, University of Pennsylvania, United States
Abstract
Steroid hormones are attractive candidates for transmitting long-range signals to affect behavior. These lipid-soluble molecules derived from dietary cholesterol easily penetrate the brain and act through nuclear hormone receptors (NHRs) that function as transcription factors. To determine the extent to which NHRs affect sleep: wake cycles, we knocked down each of the 18 highly conserved NHRs found in Drosophila adults and report that the ecdysone receptor (EcR) and its direct downstream NHR Eip75B (E75) act in glia to regulate the rhythm and amount of sleep. Given that ecdysone synthesis genes have little to no expression in the fly brain, ecdysone appears to act as a long-distance signal and our data suggest that it enters the brain more at night. Anti-EcR staining localizes to the cortex glia in the brain and functional screening of glial subtypes revealed that EcR functions in adult cortex glia to affect sleep. Cortex glia are implicated in lipid metabolism, which appears to be relevant for actions of ecdysone as ecdysone treatment mobilizes lipid droplets, and knockdown of glial EcR results in more lipid droplets. In addition, sleep-promoting effects of exogenous ecdysone are diminished in lsd-2 mutant flies, which are lean and deficient in lipid accumulation. We propose that ecdysone is a systemic secreted factor that modulates sleep by stimulating lipid metabolism in cortex glia.
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All data analyzed and reported in this study are included in the manuscript, supplementary tables, and source data linked to figures.
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Funding
Howard Hughes Medical Institute
- Amita Sehgal
National Institute of Neurological Disorders and Stroke (R01NS048471)
- Amita Sehgal
National Institutes of Health (R01DK120757)
- Amita Sehgal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ecdysone acts through cortex glia to regulate sleep in Drosophila
eLife 12:e81723.
https://doi.org/10.7554/eLife.81723
