Cell Research：LGN在小鼠卵母细胞成熟过程中的定位和功能

2009年5月12日，北京生命科学研究所高绍荣实验室在Cell Research杂志在线发表题为“Pins homolog LGN regulates meiotic spindle organization in mouse oocytes”的文章，该文章报道了LGN在小鼠卵母细胞成熟过程中的定位和功能。

小鼠卵母细胞的减数分裂是极端的细胞不对称分裂，排出的极体很小、没有明显的生物学功能，而卵母细胞却要留下大部分的母源物质以支持早期的胚胎发育。这种不对称分裂的实现需要桶状纺锤体向卵母细胞皮质区域的迁移以及皮质区域的极化。本论文研究进化上保守的Pins同源物在小鼠卵母细胞中的功能。 LGN是在小鼠卵母细胞中表达的Pins同源物。在生发泡期的卵母细胞中，LGN定位在卵母细胞质中和细胞皮质上。随着卵母细胞的成熟，细胞质中的LGN 定位在减数分裂纺锤体上，而皮质上原本均匀分布的LGN则被极化，在将来排出极体的地方特异性地消失。LGN在小鼠卵母细胞内的过量表达会导致纺锤体伸长、纺锤体两极过度收拢以及纺锤体两极?-tubulin的脱离，而LGN的下调则会导致染色体聚集排列以及纺锤体装配的缺陷。进一步的结构域分析发现 LGN的N-端区域主要负责对纺锤体形态结构的调节，而LGN C-端区域负责LGN在皮质上的定位和极化。这些发现表明LGN在卵母细胞成熟过程中参与皮质区域的极化并且在纺锤体装配过程中起重要作用。

该文章的第一作者为郭欣政，通讯作者为高绍荣博士，该项研究由科技部863项目资助。

Pins homolog LGN regulates meiotic spindle organization in mouse oocytes

Xinzheng Guo1,2 and Shaorong Gao2

1College of Life Science, Peking University, Beijing 100871, China

2National Institute of Biological Sciences, Beijing 102206, China

Mouse oocytes undergo polarization during meiotic maturation, and this polarization is essential for asymmetric cell divisions that maximize retention of maternal components required for early development. Without conventional centrosomes, the meiotic spindle has less focused poles and is barrel-shaped. The migration of meiotic spindles to the cortex is accompanied by a local reorganization and polarization of the cortex. LGN is a conserved protein involved in cell polarity and regulation of spindle organization. In the present study, we characterized the localization dynamics of LGN during mouse oocyte maturation and analyzed the effects of LGN upregulation and downregulation on meiotic spindle organization. At the germinal vesicle stage, LGN is distributed both cytoplasmically and at the cortex. During maturation, LGN localizes to the meiotic spindle apparatus and cortical LGN becomes less concentrated at the actin cap region. Excessive LGN induces meiotic spindle organization defects by elongating the spindle and enhancing pole focusing, whereas depletion of LGN by RNA interference results in meiotic spindle deformation and chromosome misalignment. Furthermore, the N-terminus of LGN has the ability of full-length LGN to regulate spindle organization, whereas the C-terminus of LGN controls cortical localization and polarization. Our results reveal that LGN is cortically polarized in mouse oocytes and is critical for meiotic spindle organization.