title: Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Leader
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Lim
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Carabatsos
authors.forename: Anne
authors.initials: A
authors.lastname: Harrington
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ecsedy
authors.forename: David
authors.initials: D
authors.lastname: Pellman
authors.forename: Richard
authors.initials: R
authors.lastname: Maas
authors.forename: Philip
authors.initials: P
authors.lastname: Leder
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D011123:Polyploidy
chemical_list: D009419:Nerve Tissue Proteins