2008年11月12日，北京生命科学研究所高绍荣实验室在Biology of Reproduction杂志在线发表题为 ADP-Ribosylation Factor 1 Regulates Asymmetric Cell Division in Female Meiosis in the Mouse的文章，报道了ADP核糖基化因子-1控制小鼠卵母细胞减数分裂中不对称分裂的新发现。
不对称分裂对于很多生理功能都至关重要，包括干细胞增殖，发育的多样性，卵的减数分裂。在哺乳动物卵母细胞的减数分裂中，卵母细胞要经过两次典型的不对称分裂产生一个体积相对大的卵和两个小的极体，这样保存了尽可能多的营养物质供胚胎发育利用。虽然已知一些小G蛋白如RAC，RAN 和 CDC42在这个过程中对极性产生和纺锤体的极性定位起一定作用，但是具体机制还不清楚。在小鼠卵细胞发育中没有哪个基因突变后可以逆转不对称分裂为均等分裂。这篇文章发现ARF1，也属于Ras小G蛋白家族，控制卵的不对称分裂。把该基因突变后，卵的第一次减数分裂发生对称分裂，产生大小相同的两个卵母细胞而没有小极体的排放。即使在体外受精或孤雌活化后第二次减数分裂同样产生两个相同大小的胚胎。同时作者证明了ARF1通过影响MAPK的活性，控制细胞骨架蛋白Tubulin的结构以及稳定性来控制纺锤体的运动从而影响卵细胞分裂极性。ARF1在小鼠减数分裂中的重要作用的发现提出了一种新的控制哺乳动物卵母细胞不对称分裂的机制。
论文的第一作者王淑芳是我所和北京师范大学联合培养的博士生。其他作者还有胡建军（博后），郭新政(博士生)，渥太华健康研究所的Johne X. Liu博士。高绍荣为文章的通讯作者。此项研究受科技部863项目(2005AA210930)资金资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Biol Reprod 2008, 10.1095/biolreprod.108.073197
ADP-Ribosylation Factor 1 Regulates Asymmetric Cell Division in Female Meiosis in the Mouse
Shufang Wang , Jianjun Hu , Xinzheng Guo , Johne X. Liu , and Shaorong Gao *
Mouse oocytes undergo two successive meiotic divisions to generate one large egg with two small polar bodies, which is essential for preserving the maternal resources to support embryonic development. Although previous studies have shown that some small GTPases, such as RAC, RAN and CDC42, play important roles in cortical polarization and spindle pole anchoring, no oocytes undergo cytokinesis when the mutant forms of these genes are expressed in mouse oocytes. Here we show that the ADP-ribosylation factor 1 (ARF1) plays an important role in regulating asymmetric cell division in mouse oocyte meiosis. Microinjection of mRNA of a dominant negative mutant form of Arf1 (Arf1T31N) into fully grown germinal vesicle oocytes led to symmetric cell division in meiosis I, generating two metaphase II (MII) oocytes of equal size. Subsequently, the two MII oocytes of equal size underwent the second round of symmetric cell division to generate a 4-cell embryo (zygote) when activated parthenogenetically or via sperm injection. Furthermore, inactivation of MAPK, but not MDK (also known as MEK), has been discovered in the ARF1 mutant oocytes, and further demonstrated that ARF1, MAPK pathway plays an important role in regulating asymmetric cell division in meiosis I. Similarly, ARF1T31N-expressing superovulated MII oocytes underwent symmetric cell division in meiosis II when activation was performed. Rotation of MII spindle for 90 degree was prohibited in ARF1T31Nexpressing MII oocytes. Taken together, our results suggest that ARF1 plays an essential role in regulating asymmetric cell division in female meiosis.Microinjection of mRNA of a dominant negative mutant form of ARF1 (ARF1T31N) into fully grown germinal vesicle oocytes led to symmetric cell division in meiosis I, generating two metaphase II (MII) oocytes of equal size. Subsequently, the two MII oocytes of equal size underwent the second round of symmetric cell division to generate a 4-cell embryo (zygote) when activated parthenogenetically or via sperm injection. Furthermore, inactivation of MAP kinase, but not MEK, has been discovered in the ARF1 mutant oocytes, and further demonstrated that ARF1, MAPK pathway plays an important role in regulating asymmetric cell division in meiosis I. Similarly, ARF1T31N-expressing superovulated MII oocytes underwent symmetric cell division in meiosis II when activation was performed. Rotation of MII spindle for 90 degree was prohibited in ARF1T31N expressing MII oocytes. Taken together, our results suggest that ARF1 plays an essential role in regulating asymmetric cell division in female meiosis.
