The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes
The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes
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DOI：
10.1073/pnas.93.14.7032
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发表时间：
1996-07-09
影响因子：
11.1
通讯作者：
VandeWoude, GF
中科院分区：
文献类型：
--
作者：
Choi, TS;Fukasawa, K;VandeWoude, GF
Mos 是丝裂原激活蛋白激酶 (MAPK) 的上游激活剂，在小鼠卵母细胞中负责中期 II 停滞。这种活性与它在非洲爪蟾卵母细胞中作为细胞生长抑制因子的组成部分的功能相比较。因此，缺乏 Mos 的雌性小鼠 (MOS(-/-)) 生育力较差，来自这些动物的卵母细胞无法在中期 II 停滞并经历孤雌激活 [Colledge, W.H., Carlton, M. B. L., Udy, G. B. & Evans, M. J. (1994) Nature (London) 370, 65-68 and Hashimoto, N., Watanabe, N., Furuta, Y.、Tamemoto, H.、Sagata, N.、Yokoyama, M.、Okazaki, K.、Nagayoshi, M.、Takeda, N.、Ikawa, Y. 和 Aizawa, S. (1994) Nature (伦敦) 370, 68-71]。在这里，我们发现成熟的 MOS(-/-) 卵母细胞在整个减数分裂过程中无法激活 MAPK，而 p34(cdc2) 激酶活性直到中期 II 晚期才正常，此时它会过早降低。从表型上看，MOS(-/-) 卵母细胞的第一次减数分裂经常类似于有丝分裂或产生异常大的极体。在这些卵母细胞中，纺锤体形状发生改变，并且纺锤体无法移位到皮质，导致卵裂平面改变。此外，第一极体持续存在而不是退化，有时会经历额外的分裂，从而为孤雌生殖提供了条件。这些研究将减数分裂纺锤体的形成和第一极体的程序性降解确定为 Mos/MAPK 途径的新的重要作用。
Mos is an upstream activator of mitogen-activated protein kinase (MAPK) and, in mouse oocytes, is responsible for metaphase II arrest. This activity has been likened to its function in Xenopus oocytes as a component of cytostatic factor. Thus, Mos-deficient female mice (MOS(-/-)) are less fertile and oocytes derived from these animals fail to arrest at metaphase II and undergo parthenogenetic activation [Colledge, W.H., Carlton, M. B. L., Udy, G. B. & Evans, M. J. (1994) Nature (London) 370, 65-68 and Hashimoto, N., Watanabe, N., Furuta, Y., Tamemoto, H., Sagata, N., Yokoyama, M., Okazaki, K., Nagayoshi, M., Takeda, N., Ikawa, Y. & Aizawa, S. (1994) Nature (London) 370, 68-71]. Here we show that maturing MOS(-/-) oocytes fail to activate MAPK throughout meiosis, while p34(cdc2) kinase activity is normal until late metaphase II when it decreases prematurely. Phenotypically, the first meiotic division of MOS(-/-) oocytes frequently resembles mitotic cleavage or produces an abnormally large polar body. In these oocytes, the spindle shape is altered and the spindle fails to translocate to the cortex, leading to the establishment of an altered cleavage plane. Moreover, the first polar body persists instead of degrading and sometimes undergoes an additional cleavage, thereby providing conditions for parthenogenesis. These studies identify meiotic spindle formation and programmed degradation of the first polar body as new and important roles for the Mos/MAPK pathway.