During development of the nervous system, approximately 50% of the neurons generated undergo apoptosis as part of a normal pruning process. The neuronal corpses must be efficiently cleared to prevent an immune system response. We demonstrated that satellite glial precursor cells are the main phagocytes in the developing dorsal root ganglia (DRG), and identified a novel engulfment receptor necessary for this engulfment, Jedi-1. Jedi-1 contains immunoreceptor tyrosine based activation motifs (ITAMs) that bind to the tyrosine kinase Syk, which is required for phagocytosis. Jedi-1 also contains an NPXY motif that is required for interaction with the adapter protein GULP, which was also necessary for engulfment. Jedi-1 associates with GULP and recruits clathrin heavy chain (CHC), which promotes actin rearrangement required for engulfment. To determine the role of Jedi-1 in vivo we generated jedi-1 -/- mice. Apoptotic neurons accumulate in the developing DRG of jedi-1 -/- mice, and the mice develop autoimmune disease including the production of autoantibodies and kidney dysfunction. The jedi-1 null mice also exhibit excessive itching which results in skin lesions. Our data suggests that this itch phenotype may be due to activation of satellite glial cells in response to defective clearance of apoptotic neurons.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-09242014-104555 |
| Date | 01 October 2014 |
| Creators | Sullivan, Chelsea Suzanne |
| Contributors | David Cortez, Bruce Carter, Alyssa Hasty, Luc Van Kaer, Scott Hiebert |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-09242014-104555/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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