THE MOS MITOGEN-ACTIVATED PROTEIN-KINASE (MAPK) PATHWAY REGULATES THESIZE AND DEGRADATION OF THE FIRST POLAR BODY IN MATURING MOUSE OOCYTES/

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 comp onent of cytostatic factor. Thus, Mos-deficient female mice (MOS(-/-)) are less fertile and oocytes derived from these animals fail to arres t 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., Ik awa, Y. & Aizawa, S. (1994) Nature (London) 370, 68-71]. Here we show that maturing MOS(-/-) oocytes fail to activate MAPK throughout meiosi s, while p34(cdc2) kinase activity is normal until late metaphase II w hen it decreases prematurely. Phenotypically, the first meiotic divisi on of MOS(-/-) oocytes frequently resembles mitotic cleavage or produc es an abnormally large polar body. In these oocytes, the spindle shape is altered and the spindle fails to translocate to the cortex, leadin g to the establishment of an altered cleavage plane. Moreover, the fir st 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 degr adation of the first polar body as new and important roles for the Mos /MAPK pathway.