During development, gradients of transcription factors regulate patterning along a body axis by activation or repression of target genes above distinct threshold levels. In the Drosophila wing, expression of genes such as spalt (sal) and optomotor-blind (omb) is restricted along the A/P axis by lateral-to-medial gradients of the transcriptional repressor Brinker (Brk). sal is more sensitive to repression by Brk than omb, and thus has a narrower expression domain compared to omb. The Brk expression pattern is established by Decapentaplegic (Dpp), a TGF-b superfamily member, which forms a complementary medial-to-lateral morphogen gradient along the (A/P) axis of the wing. We have investigated the mechanisms Brk uses to repress gene expression to gain an understanding of why some targets such as sal are more sensitive to Brk than others such as omb. Previous studies have suggested that Brk represses gene expression simply by competing with activators, but we show that Brk requires an active repression domain along with the DNA binding domain for repressor activity. Brk possesses four repression domains, but these domains are not equivalent; for example, 3R is sufficient to repress omb but not sal. Consequently, although sal and omb show quantitative differences in their response to Brk, there are qualitative differences in the mechanisms that Brk uses to repress each of these genes.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08152005-134633 |
| Date | 10 October 2005 |
| Creators | Winter, Stephanie E. |
| Contributors | Dr. A. Javier Lopez, Dr. Beth Stronach, Dr. Paula J. Grabowski, Dr. Jeffrey Brodsky, Dr. Gerard L. 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-08152005-134633/ |
| 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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