Identification of a molecular basis for the juvenile sleep state
- University of Pennsylvania, United States
- University of New Mexico, United States
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.
Data availability
RNA sequencing data deposited to the Gene Expression Omnibus (GSE147337).
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RNA-Seq of whole Drosophila brains (mid-pupal stage) with panneuronal pdm3 knockdown and controlsNCBI Gene Expression Omnibus, GSE147337.
Article and author information
Author details
Leela Chakravarti Dilley
Ricardo Linares Saldana
Mubarak Hussain Syed
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
- Leslie C Griffith, Brandeis University, United States
Version history
- Received: October 11, 2019
- Accepted: March 4, 2020
- Accepted Manuscript published: March 23, 2020 (version 1)
- Version of Record published: April 27, 2020 (version 2)
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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Identification of a molecular basis for the juvenile sleep state
eLife 9:e52676.
https://doi.org/10.7554/eLife.52676
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