Prostaglandin E2 (PGE2) influences many processes in vertebrates, including development, homeostasis, and disease through its GPCRs EP receptors 1-4. PGE2 regulates gastrulation movements during zebrafish embryogenesis, but how it does so was previously unclear, as PGE2 can affect cell adhesion, motility, proliferation, and survival. Our studies reveal that the loss of PGE2 synthesis impairs all gastrulation movements, epiboly, internalization, convergence, and extension, in part due to increased cell adhesion in the embryo. The increase of tight junctions (ZO1) and adherens junctions (E-cadherin) occurs in a germ layer-dependent fashion. In the mesendoderm, PGE2 modulates E-cadherin by stabilizing Snail through the inhibition of Gsk3β by a novel interaction with the Gβγ subunits (in collaboration with K. Jernigan and E. Lee). Moreover, the reduction of PGE2 synthesis results in an endoderm deficiency without significant effect on the mesoderm, possibly due to decreased Nodal signaling. Finally, we present preliminary characterization of a fish harboring a reverse genetics TILLING-generated ep4a nonsense mutation that strongly depletes function of the gene, but manifests no apparent phenotype. In conclusion, our findings suggest that PGE2 signaling can coordinate cell fate specification and movement, in part through its negative regulation of cell adhesion in zebrafish gastrulae.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-09082009-142505 |
| Date | 11 September 2009 |
| Creators | Speirs, Christina Koo Yang |
| Contributors | Joshua T. Gamse, Douglas P. Mortlock, Bruce Appel, James G. Patton, Lilianna Solnica-Krezel |
| 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-09082009-142505/ |
| 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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