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Identification of multiple roles for Wnt signaling during mouse development

Posted on:2005-07-26Degree:Ph.DType:Dissertation
University:McGill University (Canada)Candidate:Mohamed, OthmanFull Text:PDF
GTID:1454390008985029Subject:Biology
Abstract/Summary:
Signaling molecules play essential roles in communication between cells. Wnt signaling molecules are critical for embryonic development of several organisms. I examined the involvement of Wnt signaling during two major developmental processes, namely embryo implantation and formation of the embryonic body axes. Using RT-PCR analysis, I showed that multiple Wnt genes are expressed in the blastocyst at the time of implantation. Moreover, expression of Wnt 11 requires both estrogen produced by the mother and the uterine environment. Using a transgenic approach, I showed that beta-catenin-regulated transcriptional activity, which is a major transducer of Wnt signaling, is activated in the uterus specifically at the site of implantation in an embryo-dependent manner. These results introduce Wnts as candidate signaling factors that may mediate the communication between the embryo and uterus that initiates implantation.;Wnt/beta-catenin signaling triggers axis formation in Xenopus and zebrafish embryos. I showed that, during embryonic development, beta-catenin-regulated transcriptional activity is first detected in the prospective primitive streak region prior to gastrulation. This demarcates the posterior region of the embryo. This activity then becomes restricted to the elongating primitive streak and to the node. In Xenopus embryos, beta-catenin participates in the formation of the organizer through the activation of the homeodomain transcription factors Siamois and Twin. I obtained evidence that a Siamois/Twin-like binding activity exists in mouse embryos and is localized in the node. These results strongly suggest that, as the case in Xenopus and zebrafish, the Wnt/beta-catenin pathway is involved in establishing embryonic body axes.;Furthermore, using the transgenic mouse line that I generated for these studies, I mapped the transcriptional activity of beta-catenin during mouse embryonic development. These results revealed when and where this activity, and presumably Wnt signaling, is active during the development of several organs and embryonic structures.
Keywords/Search Tags:Wnt signaling, Development, Embryonic, Activity, Mouse
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