Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling
- 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.
- Science advances 5: eaax4249 (Journal)
- Registered Authors
- Prober, David
- MeSH Terms
- Animals, Genetically Modified
- ErbB Receptors/genetics*
- Evolution, Molecular
- Extracellular Signal-Regulated MAP Kinases/genetics
- Gene Expression Regulation*
- Mitogen-Activated Protein Kinases/genetics
- Signal Transduction/genetics*
- 31763451 Full text @ Sci Adv
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. (2019) Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling. Science advances. 5:eaax4249.
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes