Leader Benjamin, Lim Hyunjung, Carabatsos Mary Jo, Harrington Anne, Ecsedy Jeffrey, Pellman David, Maas Richard, Leder Philip
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA.
Nat Cell Biol. 2002 Dec;4(12):921-8. doi: 10.1038/ncb880.
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.
哺乳动物的成功繁殖需要一个有功能的卵子，它是在减数分裂过程中通过两次不对称细胞分裂形成的。在此，我们表明，最近鉴定出的一种formin同源（FH）基因，formin-2（Fmn2），是一种母体效应基因，在卵母细胞中表达，是减数分裂I中期进程所必需的。Fmn2(-/-)卵母细胞在减数分裂I期间不能正确定位中期纺锤体并形成第一极体。我们证明，Fmn2是减数分裂I中期微管非依赖性染色质定位所必需的。Fmn2(-/-)卵母细胞受精会导致多倍体胚胎形成、反复妊娠丢失以及Fmn2(-/-)雌性动物生育力低下。将Fmn2 mRNA注射到Fmn2缺陷的卵母细胞中可挽救减数分裂I阻滞。鉴于减数分裂成熟过程中的错误会导致严重的出生缺陷，并且是人类染色体非整倍性和妊娠丢失的最常见原因，对Fmn2的研究可能有助于更好地理解不孕症和出生缺陷。
