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Wnt regulation of cell motility.
~
Cohen, Ethan David.
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Wnt regulation of cell motility.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Wnt regulation of cell motility./
Author:
Cohen, Ethan David.
Description:
140 p.
Notes:
Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1149.
Contained By:
Dissertation Abstracts International65-03B.
Subject:
Biology, Molecular. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125801
ISBN:
0496730908
Wnt regulation of cell motility.
Cohen, Ethan David.
Wnt regulation of cell motility.
- 140 p.
Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1149.
Thesis (Ph.D.)--University of Pennsylvania, 2004.
Wnt proteins are a large family of secreted signaling molecules which regulate diverse cellular processes. These include changes in cell fate, gene expression, epithelial/mesenchymal transition and cell motility. Writ proteins regulate gene expression through a canonical signaling pathway that results in TCF-dependent transcription. However, the mechanisms by which Wnt proteins affect other aspects of cell behavior are less clear. My research in the laboratory of Dr. Elizabeth Wilder has focused on elucidating the mechanisms by which Wnt proteins affect cell motility.
ISBN: 0496730908Subjects--Topical Terms:
1017719
Biology, Molecular.
Wnt regulation of cell motility.
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Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1149.
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Adviser: Elizabeth L. Wilder.
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Thesis (Ph.D.)--University of Pennsylvania, 2004.
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Wnt proteins are a large family of secreted signaling molecules which regulate diverse cellular processes. These include changes in cell fate, gene expression, epithelial/mesenchymal transition and cell motility. Writ proteins regulate gene expression through a canonical signaling pathway that results in TCF-dependent transcription. However, the mechanisms by which Wnt proteins affect other aspects of cell behavior are less clear. My research in the laboratory of Dr. Elizabeth Wilder has focused on elucidating the mechanisms by which Wnt proteins affect cell motility.
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I began by characterizing an ovarian defect associated with mutations in Drosophila Wnt4 (DWnt4). DWnt4 is a divergent member of the Writ protein family which, when overexpressed, can elicit effects that are distinct from those caused by Wingless overexpression. DWnt4 mutants are both male and female sterile. In females, this sterility is associated with a morphological phenotype that results from a failure in the motility of a specific cell population. DWnt4 is expressed within this cell population and is required for its motility. Genetic analysis indicates that these cells require a specific Frizzled receptor (DFz2) and the planar polarity function of Dishevelled to receive DWnt4 signaling. In contrast, TCF-dependent transcription and the function of other planar polarity pathway components are not required. These data indicate that DWnt4 signals via a novel combination of canonical and non-canonical pathway components to regulate motility.
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At a cellular level, DWnt4 is required for the accumulation of Focal Adhesion Kinase (FAK) at the leading edges of motile cells. FAK is a regulatory kinase associated with focal adhesions, structural links between matrix bound Integrin receptors and the actin-cytoskeleton. To determine if Wnt proteins can regulate focal adhesions directly, I examined the response of NIH3T3 cells to soluble Wnt5A protein. Wnt5A treatment increases the rates of motility and focal adhesion formation relative to controls. Additionally, Wnt5A treated cells display higher numbers of actin-based cellular projections than control cells. These effects are rapid and abolished by immuno-depleting Wnt5A from the conditioned media, indicating that these are direct effects of Wnt5A signaling. Finally, Wnt5A increases the activities of Rho and Rac and blocking the functions of these small GTPases blocks the effects of Wnt5A treatment.
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School code: 0175.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125801
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