2008年11月12日，北京生命科學(xué)研究所高紹榮實(shí)驗(yàn)室在Biology of Reproduction雜志在線發(fā)表題為 ADP-Ribosylation Factor 1 Regulates Asymmetric Cell Division in Female Meiosis in the Mouse的文章,，報(bào)道了ADP核糖基化因子-1控制小鼠卵母細(xì)胞減數(shù)分裂中不對(duì)稱分裂的新發(fā)現(xiàn),。
不對(duì)稱分裂對(duì)于很多生理功能都至關(guān)重要，包括干細(xì)胞增殖,，發(fā)育的多樣性,，卵的減數(shù)分裂,。在哺乳動(dòng)物卵母細(xì)胞的減數(shù)分裂中，卵母細(xì)胞要經(jīng)過兩次典型的不對(duì)稱分裂產(chǎn)生一個(gè)體積相對(duì)大的卵和兩個(gè)小的極體,，這樣保存了盡可能多的營養(yǎng)物質(zhì)供胚胎發(fā)育利用,。雖然已知一些小G蛋白如RAC，RAN 和 CDC42在這個(gè)過程中對(duì)極性產(chǎn)生和紡錘體的極性定位起一定作用,，但是具體機(jī)制還不清楚,。在小鼠卵細(xì)胞發(fā)育中沒有哪個(gè)基因突變后可以逆轉(zhuǎn)不對(duì)稱分裂為均等分裂。這篇文章發(fā)現(xiàn)ARF1,，也屬于Ras小G蛋白家族，控制卵的不對(duì)稱分裂,。把該基因突變后,，卵的第一次減數(shù)分裂發(fā)生對(duì)稱分裂,，產(chǎn)生大小相同的兩個(gè)卵母細(xì)胞而沒有小極體的排放。即使在體外受精或孤雌活化后第二次減數(shù)分裂同樣產(chǎn)生兩個(gè)相同大小的胚胎,。同時(shí)作者證明了ARF1通過影響MAPK的活性,，控制細(xì)胞骨架蛋白Tubulin的結(jié)構(gòu)以及穩(wěn)定性來控制紡錘體的運(yùn)動(dòng)從而影響卵細(xì)胞分裂極性,。ARF1在小鼠減數(shù)分裂中的重要作用的發(fā)現(xiàn)提出了一種新的控制哺乳動(dòng)物卵母細(xì)胞不對(duì)稱分裂的機(jī)制。
論文的第一作者王淑芳是我所和北京師范大學(xué)聯(lián)合培養(yǎng)的博士生,。其他作者還有胡建軍（博后），郭新政(博士生),，渥太華健康研究所的Johne X. Liu博士,。高紹榮為文章的通訊作者。此項(xiàng)研究受科技部863項(xiàng)目(2005AA210930)資金資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
