Oocyte and Embryo Research Laboratory, Department of Cell and Developmental Biology, Division of Biosciences and Institute for Women's Health, University College London, London, UK.
Science. 2009 Nov 13;326(5955):991-4. doi: 10.1126/science.1175326.
Two critical stages of mammalian oocyte regulation are prophase I arrest, which is important for sustaining the oocyte pool, and the progression through meiosis I (MI) to produce fertilizable eggs. We have found that the spindle assembly checkpoint protein BubR1 regulates both stages in mouse oocytes. We show that oocytes depleted of BubR1 cannot sustain prophase I arrest and readily undergo germinal vesicle breakdown, a marker for reentry into MI. BubR1-depleted oocytes then arrest before completing MI, marked by failure of polar body extrusion. Both meiotic defects in BubR1-depleted oocytes are due to reduced activity of the master regulator known as the anaphase-promoting complex (APC), brought about through diminished levels of the APC coactivator Cdh1.
哺乳动物卵母细胞调控有两个关键阶段,即前期 I 阻滞,这对于维持卵母细胞池很重要,以及通过减数分裂 I(MI)的进展产生可受精的卵子。我们发现纺锤体组装检查点蛋白 BubR1 调节小鼠卵母细胞的这两个阶段。我们表明,缺乏 BubR1 的卵母细胞不能维持前期 I 阻滞,并且容易发生生发泡破裂,这是重新进入 MI 的标志。然后,BubR1 耗尽的卵母细胞在完成 MI 之前停止,标志是极体挤出失败。BubR1 耗尽的卵母细胞中的这两种减数分裂缺陷都是由于称为后期促进复合物(APC)的主调节剂的活性降低所致,这是通过 APC 共激活因子 Cdh1 的水平降低引起的。