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ucin1212062811.pdf (35.3 MB)
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Thr roles of Twist1 and Tbx20 in endocardial cell proliferation, migration, and differentiation during endocardial cushion development
Author Info
SHELTON, ELAINE L.
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212062811
Abstract Details
Year and Degree
2008, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Abstract
In the United States, congenital heart defects (CHD) are among the most common birth defects, occurring in approximately 1/100 live births. The majority of CHDs involve abnormal valvuloseptal development. Heart valvulogenesis is initiated by the formation of endocardial cushions, which will ultimately remodel into mature valve leaflets. While much is known about early events in valve development, the molecular mechanisms underlying the transition from endocardial cushion to remodeling valve leaflet remain relatively unknown. Endocardial cushions are composed of highly proliferative, migratory, undifferentiated, mesenchymal valve progenitor cells embedded in a loose extracellular matrix (ECM). The studies herein will demonstrate that robust expression of Twist1, a basic helix-loop-helix transcription factor, and Tbx20, a T-box transcription factor, in response to BMP2 signaling regulates cell proliferation, migration, and mesenchymal gene expression in endocardial cushions. In addition, these studies demonstrate that Twist1 can regulate Tbx20 expression in endocardial cushion cells. Taken together, these findings provide evidence that Twist1 acts upstream of Tbx20 and functions as a high-level regulatory protein in mesenchymal cell proliferation, migration, and differentiation in endocardial cushions. The studies presented in this dissertation identify molecular pathways that govern heart valve development and provide insight into potential therapeutic avenues for those afflicted with congenital valve defects or adult valve disease.
Committee
Katherine Yutzey, PhD (Committee Chair)
D. Woodrow Benson, MD, PhD (Committee Member)
Jo El Schultz, PhD (Committee Member)
Timothy Weaver, PhD (Committee Member)
James Wells, PhD (Committee Member)
Pages
201 p.
Subject Headings
Biomedical Research
;
Molecular Biology
Keywords
Twist1
;
Tbx20
;
endocardial cushion
;
development
;
chicken
;
heart
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Citations
SHELTON, E. L. (2008).
Thr roles of Twist1 and Tbx20 in endocardial cell proliferation, migration, and differentiation during endocardial cushion development
[Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212062811
APA Style (7th edition)
SHELTON, ELAINE.
Thr roles of Twist1 and Tbx20 in endocardial cell proliferation, migration, and differentiation during endocardial cushion development.
2008. University of Cincinnati, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212062811.
MLA Style (8th edition)
SHELTON, ELAINE. "Thr roles of Twist1 and Tbx20 in endocardial cell proliferation, migration, and differentiation during endocardial cushion development." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212062811
Chicago Manual of Style (17th edition)
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Document number:
ucin1212062811
Download Count:
367
Copyright Info
© 2008, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.