Denhart, Mariah H.
(2024)
Characterization of phenotypes resulting from the ectopic expression of T and Tbx6 in the developing limb of Mus musculus and Drosophila melanogaster.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Members of the evolutionarily conserved T-box transcription factor family share a similar DNA binding domain (T-domain) and thus have the potential to recognize similar DNA sequences in target genes. Outside of this T-domain the proteins are diverse suggesting that they function differently to regulate transcription. Interestingly, several human T-box genes show haploinsufficiency, including Tbx5 and Tbx3 that when mutated cause Holt-Oram and ulnar- mammary syndrome, respectively. This dosage sensitivity combined with the shared T-domain lead to our hypothesis that when co-expressed a competition between T-box factors at target genes can occur. I used the mouse and Drosophila limb systems to investigate the effect of artificially changing the relative levels of T-box proteins expressed in the developing limbs by ectopically expressing T or Tbx6. I characterized the phenotypes in both model systems. In the mouse, ectopic T and Tbx6 resulted in a smaller limb and skeletal defects reminiscent of hypomorphic Tbx5 limbs, and yet the Tbx6 limbs exhibited a digit duplication that is not present in T limbs. The Drosophila wing is sensitive to the levels of the Tbx2 ortholog omb. Using the GAL4/UAS system we have ectopically expressed either mouse T or Tbx6 in the developing wing disc and observed different adult wing phenotypes depending on the T-box expressed. To further examine the potential mechanism causing these different phenotypes and to understand the relationship between T-box family members, I have initiated studies to ectopically express both activating and repressive versions of T and Tbx6.
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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Unpublished |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: |
10 January 2024 |
| Date Type: |
Publication |
| Defense Date: |
27 November 2023 |
| Approval Date: |
10 January 2024 |
| Submission Date: |
2 December 2023 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
85 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
transcription factors, Tbx6, T, Brachyury, mouse limb, drosophila wing |
| Date Deposited: |
10 Jan 2024 14:48 |
| Last Modified: |
10 Jan 2024 14:48 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/45595 |
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