1. Genetics and Genomics
  2. Neuroscience
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Identification of a molecular basis for the juvenile sleep state

  1. Leela Chakravarti Dilley
  2. Milan Szuperak
  3. Naihua N Gong
  4. Charlette E Williams
  5. Ricardo Linares Saldana
  6. David S Garbe
  7. Mubarak Hussain Syed
  8. Rajan Jain
  9. Matthew S Kayser  Is a corresponding author
  1. University of Pennsylvania, United States
  2. University of New Mexico, United States
Research Article
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Cite this article as: eLife 2020;9:e52676 doi: 10.7554/eLife.52676

Abstract

Across species, sleep in young animals is critical for normal brain maturation. The molecular determinants of early life sleep remain unknown. Through an RNAi-based screen, we identified a gene, pdm3, required for sleep maturation in Drosophila. Pdm3, a transcription factor, coordinates an early developmental program that prepares the brain to later execute high levels of juvenile adult sleep. PDM3 controls the wiring of wake-promoting dopaminergic (DA) neurites to a sleep-promoting region, and loss of PDM3 prematurely increases DA inhibition of the sleep center, abolishing the juvenile sleep state. RNA-Seq/ChIP-Seq and a subsequent modifier screen reveal that pdm3 represses expression of the synaptogenesis gene Msp300 to establish the appropriate window for DA innervation. These studies define the molecular cues governing sleep behavioral and circuit development, and suggest sleep disorders may be of neurodevelopmental origin.

Article and author information

Author details

  1. Leela Chakravarti Dilley

    Department of Psychiatry, Perelman School of Medicine, 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:" 0000-0001-8115-6821
  2. Milan Szuperak

    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Naihua N Gong

    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Charlette E Williams

    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ricardo Linares Saldana

    Department of Medicine, Perelman School of Medicine, 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:" 0000-0003-2657-825X
  6. David S Garbe

    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Mubarak Hussain Syed

    Department of Biology, University of New Mexico, Albuquerque, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2424-175X
  8. Rajan Jain

    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthew S Kayser

    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    kayser@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2359-4967

Funding

National Institutes of Health (K08 NS090461)

  • Matthew S Kayser

National Institutes of Health (DP2 NS111996)

  • Matthew S Kayser

National Institutes of Health (T32 HL007953)

  • Leela Chakravarti Dilley

National Institutes of Health (F31 NS105447)

  • Leela Chakravarti Dilley

Burroughs Wellcome Fund

  • Rajan Jain

Burroughs Wellcome Fund

  • Matthew S Kayser

March of Dimes Foundation

  • Matthew S Kayser

Alfred P. Sloan Foundation

  • Matthew S Kayser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Leslie C Griffith, Brandeis University, United States

Publication history

  1. Received: October 11, 2019
  2. Accepted: March 4, 2020
  3. Accepted Manuscript published: March 23, 2020 (version 1)

Copyright

© 2020, Chakravarti Dilley 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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