Evidence map›Paper›PMID 24631345›Full record

ArticleNeuron2014

WIDE AWAKE mediates the circadian timing of sleep onset.

Sha Liu, Angelique Lamaze, Qili Liu, Masashi Tabuchi, Yong Yang, Melissa Fowler, Rajnish Bharadwaj, Julia Zhang, Joseph Bedont, Seth Blackshaw and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 156 citations in OpenAlex.

  1. Metaplastic sleep regulation inbioRxiv : the preprint server for biology · 2026
    Article
  2. 25 years ofFly · 2025
    Review
  3. Article
  4. Article
  5. mWAKE in the Central Amygdala Regulates Fear Learning and Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  6. A Subcircuit in the Suprachiasmatic Nucleus Generates Wakefulness.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Fly into tranquility: GABA's role in Drosophila sleep.Current opinion in insect science · 2024
    Review
  13. Article
  14. Article
  15. Tob Regulates the Timing of Sleep Onset at Night inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Orthologs ofSleep advances : a journal of the Sleep Research Society · 2024
    Article
  20. Review

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Sha LiuDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Angelique LamazeDepartment of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Qili LiuDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Masashi TabuchiDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Yong YangDepartment of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Melissa FowlerDepartment of Biological Chemistry, Johns Hopkins University, Baltimore, MD 21287, USA.
Rajnish BharadwajDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Julia ZhangDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Joseph BedontDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA.
Seth BlackshawDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA.
Thomas E LloydDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA.
Craig MontellNeuroscience Research Institute and Department of Molecular, Cellular, & Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Amita SehgalHoward Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kyunghee KohDepartment of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: kyunghee.koh@jefferson.edu.
Mark N WuDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: marknwu@jhmi.edu.
Johns Hopkins University · USThomas Jefferson University · USJefferson Hospital for Neuroscience · USUniversity of California, Santa Barbara · USUniversity of Pennsylvania · US

Funding

Murine Mutagenesis CoreP30NS050274 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOLODKIN, ALEX L · 2005 to 2020
$10.9M
Genetic Analysis of Sleep RegulationR01NS079584 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WU, MARK N · 2012 to 2020
$3.2M
TRPA1: a polymodal sensor for aversive stimuliR01GM085335 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI MONTELL, CRAIG · 2008 to 2015
$2.8M
Dynactin function in axons, synapses, and neurodegenerative diseaseR01NS082563 · NINDS · JOHNS HOPKINS UNIVERSITY · PI LLOYD, THOMAS E. · 2013 to 2017
$1.8M
Function of SLEEPLESS in sleep regulationR01GM088221 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOH, KYUNGHEE · 2009 to 2013
$1.4M
Genetic and phenotypic characterization of catnap, a novel short-sleeping mutantK08NS059671 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI WU, MARK N · 2008 to 2012
$864k
NIGMS NIH HHS R01 GM085335NIGMS NIH HHS R01GM085335NIGMS NIH HHS R01 GM088221NIGMS NIH HHS R01GM088221NINDS NIH HHS K08 NS059671NINDS NIH HHS K08NS059671NINDS NIH HHS P30 NS050274NINDS NIH HHS R01 NS079584NINDS NIH HHS R01NS079584NINDS NIH HHS R01 NS082563Wellcome Trust
6 · The paper itself

Abstract

How the circadian clock regulates the timing of sleep is poorly understood. Here, we identify a Drosophila mutant, wide awake (wake), that exhibits a marked delay in sleep onset at dusk. Loss of WAKE in a set of arousal-promoting clock neurons, the large ventrolateral neurons (l-LNvs), impairs sleep onset. WAKE levels cycle, peaking near dusk, and the expression of WAKE in l-LNvs is Clock dependent. Strikingly, Clock and cycle mutants also exhibit a profound delay in sleep onset, which can be rescued by restoring WAKE expression in LNvs. WAKE interacts with the GABAA receptor Resistant to Dieldrin (RDL), upregulating its levels and promoting its localization to the plasma membrane. In wake mutant l-LNvs, GABA sensitivity is decreased and excitability is increased at dusk. We propose that WAKE acts as a clock output molecule specifically for sleep, inhibiting LNvs at dusk to promote the transition from wake to sleep.

Indexed as

AnimalsAnimals, Genetically ModifiedARNTL Transcription FactorsBrainCircadian RhythmCircadian Rhythm Signaling Peptides and ProteinsCLOCK ProteinsDrosophilaDrosophila ProteinsGreen Fluorescent ProteinsHormone AntagonistsLuminescent ProteinsMifepristoneMutationNeuronsReaction TimeARNTL Transcription FactorsCircadian Rhythm Signaling Peptides and ProteinsClk protein, DrosophilaCLOCK Proteinscyc protein, DrosophilaDrosophila ProteinsGreen Fluorescent ProteinsHormone AntagonistsLuminescent ProteinsMifepristoneWake protein, Drosophila

Identifiers

PMID24631345
PMCPMC3982794
OpenAlexW2137867563

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.