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Nature Cell Biology 4, 921–928 (1 December 2002) | doi:10.1038/ncb880

Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes

Benjamin Leader , Hyunjung Lim , Mary Jo Carabatsos , Anne Harrington , Jeffrey Ecsedy , David Pellman , Richard Maas & Philip Leder

Successful reproduction in mammals requires a competent egg, which is formed during meiosis through two assymetrical cell divisions. Here, we show that a recently identified formin homology (FH) gene, formin-2 (Fmn2), is a maternal-effect gene that is expressed in oocytes and is required for progression through metaphase of meiosis I. Fmn2|[minus]|/|[minus]| oocytes cannot correctly position the metaphase spindle during meiosis I and form the first polar body. We demonstrate that Fmn2 is required for microtubule-independent chromatin positioning during metaphase I. Fertilization of Fmn2|[minus]|/|[minus]| oocytes results in polyploid embryo formation, recurrent pregnancy loss and sub-fertility in Fmn2|[minus]|/|[minus]| females. Injection of Fmn2 mRNA into Fmn2-deficient oocytes rescues the metaphase I block. Given that errors in meiotic maturation result in severe birth defects and are the most common cause of chromosomal aneuploidy and pregnancy loss in humans, studies of Fmn2 may provide a better understanding of infertility and birth defects.