DAF-16/FOXO regulates homeostasis of essential sleep-like behavior during larval transitions in C. elegans

Curr Biol. 2013 Mar 18;23(6):501-6. doi: 10.1016/j.cub.2013.02.009. Epub 2013 Mar 7.


Sleep homeostasis, which refers to the maintenance of sleep amount or depth following sleep deprivation, indicates that sleep and sleep-like states serve fundamental functions that cannot be bypassed [1]. Homeostasis of sleep-like behavior is observed during C. elegans lethargus, a 2-3 hr behavioral quiescent period that occurs during larval state transitions [2]. Here, we report a role for DAF-16/FOXO, a transcription factor that is active under conditions of stress [3], in the response to deprivation of lethargus quiescence. Forced locomotion during lethargus results in nuclear translocation of DAF-16. The formation of dauer larvae, a developmental state promoted by daf-16, is increased in response to quiescence deprivation. daf-16 mutants show an impaired homeostatic response to deprivation of lethargus quiescence and are hypersensitive to the lethal effects of forced locomotion during lethargus. DAF-16 expression in muscle cells, but not in neurons, is sufficient to restore a homeostatic response to deprivation of quiescence, pointing to a role for muscle in sleep homeostasis. These findings are relevant to clinical observations of altered metabolic signaling in response to sleep deprivation and suggest that these signaling pathways may act in nonneuronal tissue to regulate sleep behaviors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental*
  • Homeostasis
  • Larva / genetics
  • Larva / growth & development
  • Larva / physiology
  • Locomotion
  • Muscle, Skeletal / metabolism
  • Signal Transduction
  • Sleep
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Transcription Factors
  • daf-16 protein, C elegans