During liver development, precise signaling is required to direct cell fate decisions and architectural establishment. It is hypothesized that the same signaling pathways are important in directing liver regeneration. To examine the signals important in liver development and disease, we genetically manipulated Recombination signaling binding protein J kappa (Rbpj) and Hepatocyte nuclear factor 6 (Hnf6), or Vascular endothelial growth factor (Vegf) within the liver epithelium embryonically in mice. Along with these genetic models, we also examined several non-genetic rodent liver injury models and assessed the protein localization and tissue architecture of both epithelial and endothelial structures in the liver. We find that Rpbj and Hnf6 are together required for the embryonic formation of the intrahepatic bile duct, but dispensable for its regeneration postnatally. In both genetic and non-genetic cholestatic liver injuries in rodent models and in human liver disease, the expression of Sry-related HMG box 9 (Sox9) was found to be a marker of non-proliferative hepatobiliary intermediate cells that may aid the regenerative process. We also determined that the epithelial secretion of Vegf is required for proper endothelial and epithelial cell maturation and tissue architecture. These studies implicate a number of signaling relationships required for proper liver development and regeneration.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12022013-130113 |
| Date | 09 December 2013 |
| Creators | Walter, Teagan Jo |
| Contributors | Stacey Huppert, Chin Chiang, Scott Baldwin, Al Powers, Andrea Page-McCaw |
| 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-12022013-130113/ |
| 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 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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