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Abstract

We report that gene silencing via intracytoplasmic microinjections of morpholino-modified antisense oligonucleotides is an effective and reproducible method to study both maternal and zygotic gene functions during early and late stages of mouse preimplantation development. The zygotic expression of the β-geo transgene in the ROSA26 mouse strain could be inhibited until at least the early blastula stages. Thus morpholino-triggered gene inactivation appears to be a useful method to study the functional role of genes in preimplantation development. Using this approach, we have investigated a potential role of maternal expression of Cdh1, the gene encoding the cell-adhesion molecule E-cadherin. Inhibition of translation of maternal E-cadherin mRNA causes a developmental arrest at the two-cell stage. BrUTP incorporation assays indicated that this developmental defect cannot be explained by a general failure in transcriptional activity. This defect is reversible since E-cadherin mRNA can rescue the affected embryos, suggesting that a functional adhesion complex, present at the junction between blastomeres, is a prerequisite for the normal development of the mouse preimplantation embryo. Our study thus reveals a previously unanticipated role of maternal E-cadherin during early stages of mouse development.