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Competition Between T-box Transcription Factors Contributes to Developmental Dynamics of the Mouse Embryo

Wehn, Amy Kristen (2010) Competition Between T-box Transcription Factors Contributes to Developmental Dynamics of the Mouse Embryo. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Wehn, Amy Kristenakmst21@pitt.eduAKMST21
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairChapman, Deborahdlc7@pitt.eduDLC7
Committee MemberCampbell, Gerardcamp@pitt.eduCAMP
Committee MemberHildebrand, Jefferyjeffh@pitt.eduJEFFH
Committee MemberTsang, Michaeltsang@pitt.eduTSANG
Committee MemberGrabowski, Paulapag4@pitt.eduPAG4
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:, etd-07222010-165121
Date Deposited: 10 Nov 2011 19:53
Last Modified: 15 Nov 2016 13:46


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