Sonic hedgehog (Shh) signaling regulates critical processes during embryonic development and
in homeostasis of adult tissues. Deregulated pathway activity is a major factor underlying the
etiology of numerous developmental disorders and cancers. In this dissertation, I investigated
early neonatal cerebellar development, where I identified that the Purkinje neuron utilizes bidirectional
distribution of Shh to centrally regulate neurogenesis, and to expand a previously
unappreciated stem cell progenitor cell lineage in the white matter niche. Additionally, I
established a novel mouse model for a soft tissue sarcoma, Ewings sarcoma. These findings
provide new understanding of how the Purkinje neuron oversees cerebellar development, as well
as key insight into the molecular underpinnings of a Shh-driven sarcoma variant.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04162014-131844 |
| Date | 30 April 2014 |
| Creators | Fleming, Jonathan Tyler |
| Contributors | Andrea Page-McCaw, David Miller, PhD, Anna Means, PhD, James R Goldenring, MD. PhD |
| 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-04162014-131844/ |
| 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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