PUBLICATION

Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling

Authors
Lee, D.A., Liu, J., Hong, Y., Lane, J.M., Hill, A.J., Hou, S.L., Wang, H., Oikonomou, G., Pham, U., Engle, J., Saxena, R., Prober, D.A.
ID
ZDB-PUB-191126-6
Date
2019
Source
Science advances   5: eaax4249 (Journal)
Registered Authors
Prober, David
Keywords
none
MeSH Terms
  • Sleep/genetics*
  • Signal Transduction/genetics*
  • Extracellular Signal-Regulated MAP Kinases/genetics
  • Evolution, Molecular
  • Zebrafish/genetics*
  • Mitogen-Activated Protein Kinases/genetics
  • Animals, Genetically Modified
  • Animals
  • Humans
  • Gene Expression Regulation*
  • Neuropeptides/genetics*
  • ErbB Receptors/genetics*
(all 12)
PubMed
31763451 Full text @ Sci Adv
Abstract
The genetic bases for most human sleep disorders and for variation in human sleep quantity and quality are largely unknown. Using the zebrafish, a diurnal vertebrate, to investigate the genetic regulation of sleep, we found that epidermal growth factor receptor (EGFR) signaling is necessary and sufficient for normal sleep levels and is required for the normal homeostatic response to sleep deprivation. We observed that EGFR signaling promotes sleep via mitogen-activated protein kinase/extracellular signal-regulated kinase and RFamide neuropeptide signaling and that it regulates RFamide neuropeptide expression and neuronal activity. Consistent with these findings, analysis of a large cohort of human genetic data from participants of European ancestry revealed that common variants in genes within the EGFR signaling pathway are associated with variation in human sleep quantity and quality. These results indicate that EGFR signaling and its downstream pathways play a central and ancient role in regulating sleep and provide new therapeutic targets for sleep disorders.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ct845
    Small Deletion
    ct853TgTransgenic Insertion
      ct868
        Small Deletion
        ct869
          Indel
          ct870
            Indel
            ct871TgTransgenic Insertion
              ct872TgTransgenic Insertion
                zf12TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  egfCRISPR1-egfCRISPR
                  egfraCRISPR2-egfraCRISPR
                  tgfaTALEN1-tgfaTALEN
                  1 - 3 of 3
                  Show
                  Fish
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  GCaMPEFGGCaMP
                  TomatoEFGTomato
                  1 - 2 of 2
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                  Mapping
                  No data available