C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence

Background: The conserved DOS-motif proteins OSM-7 and OSM-11 function as coligands with canonical DSL (Delta, Serrate, and LAG-2) ligands to activate C. elegans Notch receptors during development. We report here that Notch ligands, coligands, and the receptors LIN-12 and GLP-1 regulate two C. eleg...

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Main Authors: Singh, Komudi, Chao, Michael Y., Somers, Gerard A., Komatsu, Hidetoshi, Corkins, Mark E., Larkins-Ford, Jonah, Tucey, Tim, Dionne, Heather M., Walsh, Melissa B., Beaumont, Emma K., Hart, Douglas, Lockery, Shawn R., Hart, Anne C.
Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering
Format: Article
Language:en_US
Published: Elsevier B.V. 2014
Online Access:http://hdl.handle.net/1721.1/92490
https://orcid.org/0000-0002-8924-0849
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author Singh, Komudi
Chao, Michael Y.
Somers, Gerard A.
Komatsu, Hidetoshi
Corkins, Mark E.
Larkins-Ford, Jonah
Tucey, Tim
Dionne, Heather M.
Walsh, Melissa B.
Beaumont, Emma K.
Hart, Douglas
Lockery, Shawn R.
Hart, Anne C.
author2 Massachusetts Institute of Technology. Department of Mechanical Engineering
author_facet Massachusetts Institute of Technology. Department of Mechanical Engineering
Singh, Komudi
Chao, Michael Y.
Somers, Gerard A.
Komatsu, Hidetoshi
Corkins, Mark E.
Larkins-Ford, Jonah
Tucey, Tim
Dionne, Heather M.
Walsh, Melissa B.
Beaumont, Emma K.
Hart, Douglas
Lockery, Shawn R.
Hart, Anne C.
author_sort Singh, Komudi
collection MIT
description Background: The conserved DOS-motif proteins OSM-7 and OSM-11 function as coligands with canonical DSL (Delta, Serrate, and LAG-2) ligands to activate C. elegans Notch receptors during development. We report here that Notch ligands, coligands, and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results: C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals, thereby regulating octanol avoidance response. In adult animals, overexpression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling alters basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies reveal that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions: Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans, suggesting that Notch may regulate sleep in other species.
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spelling mit-1721.1/924902022-09-23T14:09:37Z C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence Singh, Komudi Chao, Michael Y. Somers, Gerard A. Komatsu, Hidetoshi Corkins, Mark E. Larkins-Ford, Jonah Tucey, Tim Dionne, Heather M. Walsh, Melissa B. Beaumont, Emma K. Hart, Douglas Lockery, Shawn R. Hart, Anne C. Massachusetts Institute of Technology. Department of Mechanical Engineering Hart, Douglas Background: The conserved DOS-motif proteins OSM-7 and OSM-11 function as coligands with canonical DSL (Delta, Serrate, and LAG-2) ligands to activate C. elegans Notch receptors during development. We report here that Notch ligands, coligands, and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results: C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals, thereby regulating octanol avoidance response. In adult animals, overexpression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling alters basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies reveal that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions: Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans, suggesting that Notch may regulate sleep in other species. National Institutes of Health (U.S.) (NIH R15 DA021667-01) Massachusetts General Hospital (Medical Discovery Fund) National Institutes of Health (U.S.) (NS055813) National Institutes of Health (U.S.) (grant NIH R01 GM078171) National Institutes of Health (U.S.) (grant NIH MH051383) National Institutes of Health (U.S.) (grant NIH RC1AI087059) 2014-12-23T21:34:26Z 2014-12-23T21:34:26Z 2011-05 2010-12 Article http://purl.org/eprint/type/JournalArticle 09609822 http://hdl.handle.net/1721.1/92490 Singh, Komudi, Michael Y. Chao, Gerard A. Somers, Hidetoshi Komatsu, Mark E. Corkins, Jonah Larkins-Ford, Tim Tucey, et al. “C. Elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence.” Current Biology 21, no. 10 (May 2011): 825–834. © 2011 Elsevier Ltd. https://orcid.org/0000-0002-8924-0849 en_US http://dx.doi.org/10.1016/j.cub.2011.04.010 Current Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier
spellingShingle Singh, Komudi
Chao, Michael Y.
Somers, Gerard A.
Komatsu, Hidetoshi
Corkins, Mark E.
Larkins-Ford, Jonah
Tucey, Tim
Dionne, Heather M.
Walsh, Melissa B.
Beaumont, Emma K.
Hart, Douglas
Lockery, Shawn R.
Hart, Anne C.
C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title_full C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title_fullStr C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title_full_unstemmed C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title_short C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence
title_sort c elegans notch signaling regulates adult chemosensory response and larval molting quiescence
url http://hdl.handle.net/1721.1/92490
https://orcid.org/0000-0002-8924-0849
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