Article abstract
Nature Cell Biology 4, 921 - 928 (2002)
Published online: 25 November 2002 | doi:10.1038/ncb880
Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes
Benjamin Leader1, Hyunjung Lim2,4, Mary Jo Carabatsos3, Anne Harrington1, Jeffrey Ecsedy1, David Pellman3, Richard Maas2 & Philip Leder1
Abstract
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-/- 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-/- oocytes results in polyploid embryo formation, recurrent pregnancy loss and sub-fertility in Fmn2-/- 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.
- Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA
- Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Boston, MA 02115, USA
- Dana Farber Cancer Institute, Department of Pediatric Oncology, Boston, MA 02115, USA
- OB/GYN & Cell Biology/Physiology Washington University School of Medicine, Campus Box 8064, Maternity 603, 4566 Scott Avenue St Louis, MO 63110, USA
Correspondence to: Philip Leder1 e-mail: leder@rascal.med.harvard.edu
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