title: DAF-16/FOXO regulates homeostasis of essential sleep-like behavior during larval transitions in C. elegans.
abstract: 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.
authors.affiliation: Department of Neurology, Perelman School of Medicine and the Center for Sleep and Circadian Neurobiology, University of Pennsylvania, 462 Stemmler Hall, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Driver
authors.forename: Annesia L
authors.initials: AL
authors.lastname: Lamb
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wyner
authors.forename: David M
authors.initials: DM
authors.lastname: Raizen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D008124:Locomotion; D018482:Muscle, Skeletal / Q000378:metabolism; D015398:Signal Transduction; D012890:Sleep; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans