The roles of Wnt genes in the development of the mouse female reproductive tract.
Item
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Title
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The roles of Wnt genes in the development of the mouse female reproductive tract.
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Identifier
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AAI9917679
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identifier
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9917679
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Creator
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Miller, Elizabeth Cary.
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Contributor
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Adviser: David A. Sassoon
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Cell | Biology, Genetics | Biology, Animal Physiology
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Abstract
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The murine female reproductive tract differentiates during postnatal development in response to specific mesenchymal-epithelial interactions and changing levels of circulating steroid hormones. The expression of members of the Wnt family of signaling molecules has been recently identified in this system. The expression patterns of Wnt genes in the developing and adult female reproductive tracts are described. The Wnt gene expression patterns in the female reproductive tract suggest that Wnt genes may indeed play roles in the mesenchymal-epithelial interactions critical for female reproductive tract development and function.;Gain-of-function and loss-of-function experiments were performed to examine the roles of Wnt genes in the development and adult function of the female reproductive tract. Retrovirally-mediated ectopic expression of Wnt-1 re-directs cytodifferentiation in tissue grafts. Additionally, the roles of Wnt-7a in the female reproductive tract were evaluated in Wnt-7a null mice. A number of defects were observed which suggest that Wnt-7a functions in anterio-posterior patterning in the developing female reproductive tract. In addition to a global posterior shift in the female reproductive tract, the organization of the uterine smooth muscle is affected, indicating that development along the radial axis has also been altered. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anterior-posterior and radial axes of the female reproductive tract.;The observed phenotype of the Wnt-7a null mice closely resembles the reproductive tract morphologies observed in female mice exposed prenatally to DES. This observation raises the possibility that Wnt-7a plays a role in the response to DES. A specific molecular response to DES has not been identified that fully accounts for the DES syndrome. I propose that the observed transient down-regulation of Wnt-7a is sufficient to account for the murine DES syndrome. DES-like substances such as Tamoxifen have recently been shown to be effective in decreasing the incidence of breast cancer in premenopausal women, although uterine cancer increases by 2-fold. A better understanding of the molecular responses in breast and uterine tissues to steroidal pharmacological agents will be of high importance should their use increase in clinical applications.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
