Cell Biology

Notch and Sleep

Sci. Signal.  31 May 2011:
Vol. 4, Issue 175, pp. ec153
DOI: 10.1126/scisignal.4175ec153

Notch signaling has well-characterized roles in development and specification of cell fate; however, Notch also plays nondevelopmental roles in adults, such as long-term memory formation in Drosophila. Two groups now provide evidence of a role for Notch in regulating sleep in flies and worms. Singh et al. found that Caenorhabditis elegans overexpressing OSM-11, a coligand of Notch, exhibited a sleeplike quiescent state that resembled the state of lethargus that accompanies larval molting. The effects of increased OSM-11 abundance and Notch signaling in worms required the same genes that regulate lethargus. Exposure of worms to osmotic stress repressed the secretion of OSM-11. Deletion of genes encoding Notch coligands in worms reduced the extent of quiescence and increased their responsiveness. Seugnet et al. examined the role of Notch signaling in sleep regulation in flies. Sleep deprivation triggered the expression in mushroom bodies (structures in the brain involved in memory formation and sleep regulation) of bunched, which encodes a transcription factor that inhibits Notch signaling, and mutations in bunched affected sleep homeostasis, which is the compensatory increase in sleep, or “sleep rebound,” that occurs after sleep deprivation. Overexpression of the Notch ligand Delta resulted in decreased sleep rebound, as did expression of a gain-of-function mutant of Notch. These data suggest that sleep deprivation, through bunched, triggers inhibition of Notch signaling to enable sleep rebound. Immunohistochemical analysis showed that Notch was found in glia and that Delta was localized to neurons. The authors also showed that enhanced Notch signaling abrogated the negative effects of sleep deprivation on learning in flies. Together, these studies suggest that Notch signaling promotes sleep in worms and inhibits the homeostatic sleep response in flies. Wu and Raizen point out that stress reduced Notch signaling in both organisms, leading them to suggest that Notch may play a conserved role in responding to stress, although the outcomes of the responses may be species-specific.

L. Seugnet, Y. Suzuki, G. Merlin, L. Gottschalk, S. P. Duntley, P. J. Shaw, Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila. Curr. Biol. 21, 835–840 (2011). [PubMed]

K. Singh, M. Y. Chao, G. A. Somers, H. Komatsu, M. E. Corkins, J. Larkins-Ford, T. Tucey, H. M. Dionne, M. B. Walsh, E. K. Beaumont, D. P. Hart, S. R. Lockery, A. C. Hart, C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence. Curr. Biol. 21, 825–834 (2011). [PubMed]

M. N. Wu, D. M. Raizen, Notch signaling: A role in sleep and stress. Curr. Biol. 21, R397–R398 (2011). [PubMed]