Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes.
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.
Leader
Benjamin
B
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA.
Lim
Hyunjung
H
Carabatsos
Mary Jo
MJ
Harrington
Anne
A
Ecsedy
Jeffrey
J
Pellman
David
D
Maas
Richard
R
Leder
Philip
P
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
D009419:Nerve Tissue Proteins