Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published August 7, 2023 | Published
Journal Article Open

The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation


Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na⁺,K⁺-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na⁺,K⁺-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na⁺ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na⁺ pump function modulates neuronal excitability to maintain normal sleep behaviour.

Copyright and License

© 2023, Barlow et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


The initial screen, discovery, and characterisation of dreammist were conducted in the lab of Alexander F Schier at Harvard University. We also would like to thank members of the Rihel lab and other UCL zebrafish groups for helpful comments on experiments and the article. We thank Shannon Shibata-Germanos for fxyd1 mutant tracking experiments, John Parnavalas for reagents, Christine Orengo for help with small peptide sequence searches, Stuart Peirson for early access to mouse transcriptomic data, and Finn Mango Bamber for the Pokémon-card-inspired dreammist name. The work was funded by NIH grants awarded to Alexander Schier (GM085357 and HL10952505); an ERC Starting Grant (#282027) and Wellcome Trust Investigator Award (#217150/Z/19/Z) to JR; NIH grant R35 NS122172 to DAP; and a Grand Challenges PhD studentship to ILB.


Ida L Barlow, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing – original draft, Writing – review and editing; Eirinn Mackay, Resources, Data curation, Formal analysis; Emily Wheater, Data curation, Formal analysis, Investigation, Methodology; Aimee Goel, Formal analysis, Investigation; Sumi Lim, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing – review and editing; Steve Zimmerman, Resources, Data curation, Investigation, Methodology; Ian Woods, Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing; David A Prober, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing; Jason Rihel, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing – original draft, Project administration, Writing – review and editing

Data Availability

Data on gene selection is included in Figure 1—source data 1. Software used to analyze data are available at https://github.com/ilbarlow/Dmist (copy archived at Barlow, 2020) and https://github.com/JRihel/Sleep-Analysis/tree/Sleep-Analysis-Code (copy archived at Rihel, 2023). All fish lines are listed in Table 1 and sperm are frozen at UCL, available upon request. Primers used in this study are listed in Table 2. Tracking data used to generate the figures in this article are available at https://github.com/ilbarlow/Dmist.

The following previously published dataset was used:

Zhang Y, Chen K, Sloan SA, Scholze AR, Caneda C, Ruderisch N, Deng S, Daneman R, Barres BA, JQ Wu. 2014. An RNA-Seq transcriptome and splicing database of neurons, glia, and vascular cells of the cerebral cortex. NCBI Gene Expression Omnibus. GSE52564

Additional Information

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.


Raising of genetically altered zebrafish and all experimental procedures were performed under project licence 70/7612 and PA8D4D0E5 awarded to JR under the UK Animals (Scientific Procedures) Act 1986 guidelines.


Files (3.1 MB)
Name Size Download all
106.4 kB Download
2.7 MB Preview Download
267.5 kB Download

Additional details

November 9, 2023
January 9, 2024