Wehn, Amy Kristen
(2010)
Competition Between T-box Transcription Factors Contributes to Developmental Dynamics of the Mouse Embryo.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
1 October 2010 |
| Date Type: |
Completion |
| Defense Date: |
7 June 2010 |
| Approval Date: |
1 October 2010 |
| Submission Date: |
22 July 2010 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Mouse development; somites; T-box transcription factors |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07222010-165121/, etd-07222010-165121 |
| Date Deposited: |
10 Nov 2011 19:53 |
| Last Modified: |
15 Nov 2016 13:46 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8527 |
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