description): The molecular mechanisms that govern the earliest stages of mammalian preimplantation development remain largely unexplored because, until recently, there were no molecular probes to investigate this process. The mammalian egg is transcriptionally inert, and the embryonic genome is not immediately transcribed upon fertilization. Consequently, key development processes during this period are governed by timely translation of stored maternal transcripts and cascades of post-translational modifications. The investigators have devised a strategy to determine the function of maternal transcripts during early preimplantation development. The Cre/loxP conditional null mutagenesis where Cre-induced disruption of the genes under investigation is confined to the oocyte by the controlling sequences of the zona pellucida 3 gene. Mutation eliminates the transcription of the targeted gene in the growing oocyte so there is no maternal mRNA in the embryo. The first gene we propose to target is the cell adhesion molecule E-cadherin that mediates embryonic compaction. Previous classical knock-out studies of E-cadherin have demonstrated that the homozygous null mutants die at the time of implantation. However, the embryo compacts and survives to from the blastocyst. If E-cadherine is essential to the initiation of compaction, then it is likely synthesized from residual maternal mRNAs. Since the mutation is an embryonic lethal, the effect of the lack of its maternal mRNA could not be addressed in the offspring. An oocyte-specific knock-out experiment to study the role of maternally encodes E-cadherin in compaction will be performed.
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