Salerno, Kathleen Marie
(2011)
Identification of transcriptional targets of the nerve injury-induced transcription factor Sox11.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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).
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| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
5 August 2011 |
| Date Type: |
Completion |
| Defense Date: |
16 June 2011 |
| Approval Date: |
5 August 2011 |
| Submission Date: |
4 August 2011 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
adenomatous polyposis coli; APC; BDNF; brain-derived neurotrophic factor; JNK; Jun kinase; nerve injury; peripheral nerve injury; SoxC; TANK; TNF; TNF-alpha; transcription factor; transcriptional regulation; Sox11; SoxC |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-08042011-134001/, etd-08042011-134001 |
| Date Deposited: |
10 Nov 2011 19:57 |
| Last Modified: |
15 Nov 2016 13:48 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8894 |
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