Ecdysone acts through cortex glia to regulate sleep in Drosophila

  1. Yongjun Li
  2. Paula Haynes
  3. Shirley L Zhang
  4. Zhifeng Yue
  5. Amita Sehgal  Is a corresponding author
  1. 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.

Data availability

All data analyzed and reported in this study are included in the manuscript, supplementary tables, and source data linked to figures.

Article and author information

Author details

  1. Yongjun Li

    Chronobiology and Sleep Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Paula Haynes

    Chronobiology and Sleep Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shirley L Zhang

    Chronobiology and Sleep Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6672-2044
  4. Zhifeng Yue

    Chronobiology and Sleep Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Amita Sehgal

    Chronobiology and Sleep Institute, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    For correspondence
    amita@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7354-9641

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.

Reviewing Editor

  1. Mani Ramaswami, Trinity College Dublin, Ireland

Version history

  1. Received: July 9, 2022
  2. Preprint posted: August 26, 2022 (view preprint)
  3. Accepted: January 30, 2023
  4. Accepted Manuscript published: January 31, 2023 (version 1)
  5. Version of Record published: February 14, 2023 (version 2)

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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  1. Yongjun Li
  2. Paula Haynes
  3. Shirley L Zhang
  4. Zhifeng Yue
  5. Amita Sehgal
(2023)
Ecdysone acts through cortex glia to regulate sleep in Drosophila
eLife 12:e81723.
https://doi.org/10.7554/eLife.81723

Share this article

https://doi.org/10.7554/eLife.81723

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