Font Size: a A A

The role and regulation of the Wnt/beta-catenin pathway at the time of implantation in the mouse

Posted on:2010-06-02Degree:Ph.DType:Dissertation
University:McGill University (Canada)Candidate:Jonnaert, MaudFull Text:PDF
GTID:1444390002485936Subject:Biology
Abstract/Summary:
One of the crucial events during mammalian embryogenesis is the process of implantation. Implantation enables the embryo to invade the uterine endometrium and to gain access to the maternal circulation. The attachment reaction requires a highly coordinated dialogue between the implanting blastocyst and the receptive uterus, known as the embryo-uterine cross-talk. Since the blastocyst expresses multiple Wnt genes, in this study, we have characterized the role and regulation of the Wnt/beta-catenin pathway in embryo-uterine communication.;One possible mechanism that regulates the responsiveness of the luminal epithelium to Wnt is the regulation of components of the Wnt pathway. We show that there is dynamic pattern of expression of the components of the Wnt pathway at the time of implantation. Furthermore, we demonstrate that LIF signalling is required for the expression of a subset of these Wnt components in luminal epithelial cells at the time of implantation. Our results demonstrate that the LIF and Wnt signalling pathway form a network involved in coordinating the process of implantation.;As Wnt/beta-catenin signalling is essential for embryo attachment, we proposed that this pathway activates downstream target genes required for implantation. Using microarray analysis, we determined what are the specific target genes of the Wnt/beta-catenin pathway in the uterus. Genes up-regulated by the Wnt/beta-catenin pathway are involved m a variety of cellular processes such as cell differentiation, cell proliferation, cell cycle, cell adhesion and enzyme regulatory activity.;Despite the discovery of numerous molecules and signalling pathways involved in this process, the precise sequence and hierarchy of events leading to successful embryo implantation remains to be elucidated. Unravelling the hierarchy of events that initiates the attachment process is of clinical relevance to improve fertility and develop new contraceptives.;Using a transgenic mouse that reports Wnt signalling through the canonical pathway, we have demonstrated that the Wnt/beta-catenin pathway was transiently activated in the regions of the uterine luminal epithelium apposed to the blastocyst at the time of implantation. Activation of this pathway within the endometrium depended on the presence of the blastocyst and required the oestrogen surge. We further demonstrated that activation of the Wnt/beta-catenin pathway was essential for proper implantation to occur.
Keywords/Search Tags:Implantation, Wnt/beta-catenin pathway, Time, Regulation, Process, Genes
Related items