<it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it>
<p>Abstract</p> <p>Background</p> <p>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...
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| Format: | Article |
| Language: | English |
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BMC
2005-07-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/6/45 |
| _version_ | 1818038890154426368 |
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| author | Tucey Tim M Larkins-Ford Jonah Chao Michael Y Hart Anne C |
| author_facet | Tucey Tim M Larkins-Ford Jonah Chao Michael Y Hart Anne C |
| author_sort | Tucey Tim M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>Drosophila</it>. 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 <it>Caenorhabditis elegans lin-12 </it>Notch signaling in neurons regulating the spontaneous reversal rate during locomotion.</p> <p>Results</p> <p>The spontaneous reversal rate of <it>C. elegans </it>during normal locomotion is constant. Both <it>lin-12 </it>gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by <it>lin-12 </it>activity, because the loss of function defect could be rescued by a wild type <it>lin-12 </it>transgene. Furthermore, overexpression of <it>lin-12 </it>recapitulated the gain-of-function defect. Increasing or decreasing <it>lin-12 </it>activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for <it>lin-12</it>. Although <it>lin-12 </it>is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering <it>lin-12 </it>activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical <it>lin-12 </it>signaling cascade, including the ligand <it>lag-2 </it>and the transcriptional effector <it>lag-1</it>. Finally, the <it>C. elegans </it>AMPA/kainate glutamate receptor homolog <it>glr-1 </it>shows strong genetic interactions with <it>lin-12</it>, suggesting that <it>glr-1 </it>and/or other glutamate gated channels may be targets of <it>lin-12 </it>regulation.</p> <p>Conclusion</p> <p>Our results demonstrate a neuronal role for <it>lin-12 </it>Notch in <it>C. elegans </it>and suggest that <it>lin-12 </it>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.</p> |
| first_indexed | 2024-12-10T07:49:55Z |
| format | Article |
| id | doaj.art-330ba1d655fe44b189be23641aef1430 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-10T07:49:55Z |
| publishDate | 2005-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-330ba1d655fe44b189be23641aef14302022-12-22T01:57:03ZengBMCBMC Neuroscience1471-22022005-07-01614510.1186/1471-2202-6-45<it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it>Tucey Tim MLarkins-Ford JonahChao Michael YHart Anne C<p>Abstract</p> <p>Background</p> <p>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 <it>Drosophila</it>. 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 <it>Caenorhabditis elegans lin-12 </it>Notch signaling in neurons regulating the spontaneous reversal rate during locomotion.</p> <p>Results</p> <p>The spontaneous reversal rate of <it>C. elegans </it>during normal locomotion is constant. Both <it>lin-12 </it>gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by <it>lin-12 </it>activity, because the loss of function defect could be rescued by a wild type <it>lin-12 </it>transgene. Furthermore, overexpression of <it>lin-12 </it>recapitulated the gain-of-function defect. Increasing or decreasing <it>lin-12 </it>activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for <it>lin-12</it>. Although <it>lin-12 </it>is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering <it>lin-12 </it>activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical <it>lin-12 </it>signaling cascade, including the ligand <it>lag-2 </it>and the transcriptional effector <it>lag-1</it>. Finally, the <it>C. elegans </it>AMPA/kainate glutamate receptor homolog <it>glr-1 </it>shows strong genetic interactions with <it>lin-12</it>, suggesting that <it>glr-1 </it>and/or other glutamate gated channels may be targets of <it>lin-12 </it>regulation.</p> <p>Conclusion</p> <p>Our results demonstrate a neuronal role for <it>lin-12 </it>Notch in <it>C. elegans </it>and suggest that <it>lin-12 </it>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.</p>http://www.biomedcentral.com/1471-2202/6/45 |
| spellingShingle | Tucey Tim M Larkins-Ford Jonah Chao Michael Y Hart Anne C <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> BMC Neuroscience |
| title | <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> |
| title_full | <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> |
| title_fullStr | <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> |
| title_full_unstemmed | <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> |
| title_short | <it>lin-12 </it>Notch functions in the adult nervous system of <it>C. elegans</it> |
| title_sort | it lin 12 it notch functions in the adult nervous system of it c elegans it |
| url | http://www.biomedcentral.com/1471-2202/6/45 |
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