Tbx6 is a member of the T-box family of transcription factors that is expressed within the primitive streak and presomitic mesoderm of the developing mouse embryo and is critical for the patterning and specification of the paraxial mesoderm. This work has investigated how Tbx6 interacts with other T-box transcription factors both in its endogenous expression domain and when it is ectopically expressed. To this end, we have used a combined genetic, transcriptional, and biochemical approach to investigate potential competition between Tbx6 and T, a T-box
transcription factor co-expressed with Tbx6 in the primitive streak and tailbud. Additionally, we have developed a 3-component transgenic system to ectopically express Tbx6 outside of its endogenous domain, driving expression in the formed somites and limb buds. Three-component embryos displayed vertebral, rib, and limb anomalies resembling those in Tbx15 and Tbx18 null embryos. We showed that ectopic Tbx6 in these embryos could compete with Tbx15 and Tbx18 at the level of DNA binding. This suggested that the dynamic interplay of co-expressed T-box transcription factors might contribute to observed congenital birth defects resulting from heterozygous loss of a particular family member. While this work focused on one specific family of transcription factors, it implies that transcription factor family members that are related via a conserved DNA binding domain may also compete for downstream targets in vivo and that this then contributes to the overall developmental dynamics of the organism.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07222010-165121 |
| Date | 01 October 2010 |
| Creators | Wehn, Amy Kristen |
| Contributors | Deborah Chapman, Ph.D., Paula Grabowski, Ph.D., Michael Tsang, Ph.D., Jeffery Hildebrand, Ph.D., Gerard Campbell, Ph.D. |
| 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-07222010-165121/ |
| 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 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. |
Page generated in 0.0045 seconds