Human diseases such as spina bifida are caused by a failure in cell morphogenesis and tissue fusion. Dorsal closure in the Drosophila embryo is a model for these tissue closure processes where proper Jun N-terminal Kinase (JNK) signaling is necessary. JNK activity is required in the leading edge cells of the epithelial layer to modulate the cytoskeleton and cell shape, allowing the epidermis to close on the dorsal side of the embryo. The mixed lineage kinase (MLK), Slipper (Slpr), is the JNKKK which is responsible for activation of the pathway during dorsal closure. The pathway components that regulate Slpr, as well as upstream activation signals, are not yet identified. We have examined the involvement of the Ste20-like kinase Misshapen (Msn) to act as the JNKKKK in the JNK pathway during dorsal closure through a direct interaction between Msn and Slpr. By observing phenotypes of recombinant and heterozygous mutants of slpr and msn, we have examined the genetic interactions. Also, by using a non-biased screen, we have investigated unknown regulators of the Slpr-mediated JNK pathway which have an effect on dorsal closure. These techniques have begun to identify regulatory interactions of molecules within the JNK pathway, and have narrowed down regions of chromosome two which may contain new modifiers further regulating JNK signaling, in order to provide a robust and highly regulated tissue closure event.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08162006-123347 |
| Date | 28 September 2006 |
| Creators | Reedy, Christy M |
| Contributors | Dr. Beth Stronach, Dr. James Pipas, Dr. Jeffrey Hildebrand, Dr. Gerard Campbell |
| 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-08162006-123347/ |
| 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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