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dc.contributor.authorChao, Michael
dc.contributor.authorLarkins-Ford, Jonah
dc.contributor.authorTucey, Tim M
dc.contributor.authorHart, Anne C
dc.date.accessioned2011-05-11T02:23:55Z
dc.date.issued2005
dc.identifier.citationChao, Michael Y., Jonah Larkins-Ford, Tim M. Tucey, and Anne C. Hart. 2005. lin-12 Notch functions in the adult nervous system of C. elegans. BMC Neuroscience 6: 45.en_US
dc.identifier.issn1471-2202en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4887117
dc.description.abstractBackground: Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. Results: The spontaneous reversal rate of C. elegans during normal locomotion is constant. Both lin-12 gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by lin-12 activity, because the loss of function defect could be rescued by a wild type lin-12 transgene. Furthermore, overexpression of lin-12 recapitulated the gain-of-function defect. Increasing or decreasing lin-12 activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for lin-12. Although lin-12 is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering lin-12 activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical lin-12 signaling cascade, including the ligand lag-2 and the transcriptional effector lag-1. Finally, the C. elegans AMPA/kainate glutamate receptor homolog glr-1 shows strong genetic interactions with lin-12, suggesting that glr-1 and/or other glutamate gated channels may be targets of lin-12 regulation. Conclusion: Our results demonstrate a neuronal role for lin-12 Notch in C. elegans and suggest that lin-12 acutely regulates neuronal physiology to modulate animal behavior, without altering neuronal cell fate specification or neurite outgrowth. This is consistent with a role for Notch signaling in neurological disease with late onset symptoms.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2202-6-45en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181819/pdf/en_US
dash.licenseLAA
dc.titlelin-12 Notch functions in the adult nervous system of C. elegansen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Neuroscienceen_US
dash.depositing.authorChao, Michael
dc.date.available2011-05-11T02:23:55Z
dash.affiliation.otherSPH^Student Stipends^IIDen_US
dash.affiliation.otherSPH^Student Stipendsen_US
dash.affiliation.otherHMS^Stipendees - Div of Medical Sciencesen_US
dc.identifier.doi10.1186/1471-2202-6-45*
dash.contributor.affiliatedChao, Michael C.


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