This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mammalian oocyte-to-embryo transition depends on proteins and mRNA stored in the oocyte. In investigating the mechanisms involved in this transition, I uncovered a possible role for beta-catenin and Wnt signaling in oocyte and preimplantation embryo development. To determine the role of beta-catenin in oocyte- and preimplantation development, we (and others) conditionally eliminated this gene from mouse oocytes. Importantly, reevaluation of the deleted-floxed beta-catenin (Ctnnb1-floxed-deleted) alleles revealed that it expresses a shortened transcript, and protein. Oocytes expressing N-terminal beta-catenin give rise to embryos whose early blastomeres do not adhere (but nonetheless produce live born pups). The zona pellucida thus ensures blastomere proximity until blastomere adhesion is established upon translation of protein from the wild type paternal allele. In the absence of maternal E-cadherin, wild type and truncated beta-catenin translocate to pronuclei of the zygote and 2-cell stage embryo, thus creating an over-expression paradigm. Normal development of these embryos, however, suggests that the Wnt/beta-catenin pathway is not held inactive during the oocyte-to-embryo transition. This was further confirmed by expressing a stabilized form of beta-catenin in oocytes. Crosses with a Wnt-reporter likewise showed that the Wnt/beta-catenin pathway is inactive until completion of preimplantation embryo development. To further explore the possibility that the truncated form of beta-catenin might be important for preimplantation embryo development, we mated Ctnnb1-floxed/Ctnnb1-floxed;+/+ (control) and Ctnnb1-floxed/Ctnnb1-floxed;cre/+ females with males heterozygous for the floxed-deleted beta-catenin allele (Ctnnb1-floxed-deleted/Ctnnb1/+/+). Outcomes suggest that full-length beta-catenin is not required for preimplantation development.
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