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Characterization of phenotypes resulting from the ectopic expression of T and Tbx6 in the developing limb of Mus musculus and Drosophila melanogaster

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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Denhart, Mariah H.mad324@pitt.edumad324
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairChapman, Deborahdlc7@pitt.edudlc7
Committee MemberCampbell, Gerardcamp@pitt.educamp
Committee MemberHildebrand, Jeffjeffh@pitt.edujeffh
Committee MemberRebeiz, Markrebeiz@pitt.edurebeiz
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


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