Transcriptional regulation is an important component of the peripheral sensory neuronal response to injury. The transcription factor Sox11 is upregulated in injured dorsal root ganglion (DRG) neurons. Sox11 expression has been linked to neuronal survival and improved regeneration following nerve injury; however, its transcriptional targets are largely unknown. Towards understanding the pro-regenerative effects of Sox11, this dissertation focused on the identification of novel Sox11 transcriptional targets. Targets were initially identified via microarray screening and were validated by approaches including real-time PCR, luciferase reporter assays, western blot and chromatin immunoprecipitation (ChIP). Brain-derived neurotrophic factor (BDNF), adenomatous polyposis coli (APC) and TRAF-associated activator of NF-kappa B (TANK) were identified as putative Sox11 transcriptional targets. BDNF and APC have previously been linked to pro-regenerative pathways in DRG neurons. BDNF is a growth factor that has been shown to increase the intrinsic growth state of neurons (Geremia et al., 2010). APC is a modulator of Wnt signaling pathways and a plus-end microtubule stabilizing protein and been shown to be essential for neurite extension following peripheral axotomy (Zhou et al., 2006). TANK is a novel gene in the context of nerve regeneration signaling; my experiments show that TANK is highly expressed in dissociated DRG neuronal cultures, that TANK knockdown increased apoptosis in Neuro-2a cells following TNF-alpha stimulation and that TANK expression may modulate activation of c-Jun N-terminal kinase (JNK).
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08042011-134001 |
| Date | 05 August 2011 |
| Creators | Salerno, Kathleen Marie |
| Contributors | Dr. Kathryn Albers, Dr. Elias Aizenman, Dr. Derek Molliver, Dr. Brian Davis, Dr. Jun-Ming Zhang, Dr. Alan Sved |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-08042011-134001/ |
| Rights | unrestricted, 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 University of Pittsburgh 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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