Skip to main content Accessibility help

The Distribution and Possible Role of ERK8 in Mouse Oocyte Meiotic Maturation and Early Embryo Cleavage

  • Shang-Wu Yang (a1) (a2) (a3), Hao Huang (a3), Chen Gao (a4), Lei Chen (a2), Shu-Tao Qi (a2), Fei Lin (a2), Jian-Xin Wang (a5), Yi Hou (a2), Fu-Qi Xing (a1) and Qing-Yuan Sun (a2)...


It is well known that extracellular signal-regulated kinase 8 (ERK8) plays pivotal roles in various mitotic events. But its physiological roles in oocyte meiotic maturation remain unclear. In this study, we found that although no specific ERK8 signal was detected in oocyte at the germinal vesicle stage, ERK8 began to migrate to the periphery of chromosomes shortly after germinal vesicle breakdown. At prometaphase I, metaphase I (MI), anaphase I, telophase I, and metaphase II (MII) stages, ERK8 was stably detected at the spindles. By taxol treatment, we clarified that the ERK8 signal was stained on the spindle fibers as well as microtubule asters in MI and MII oocytes. In fertilized eggs, the ERK8 signal was not observed in the two pronuclei stages. At prometaphase, metaphase, and anaphase of the first mitosis, ERK8 was detected on the mitotic spindle. ERK8 knock down by antibody microinjection and specific siRNA caused abnormal spindles, failed chromosome congression, and decreased first polar body extrusion. Taken together, our results suggest that ERK8 plays an important role in spindle organization during mouse oocyte meiotic maturation and early embryo cleavage.


Corresponding author

* Corresponding author : E-mail:
** Corresponding author : E-mail:


Hide All
Abe, M.K., Saelzler, M.P., Espinosa, R. 3rd, Kahle, K.T., Hershenson, M.B., Le Beau, M.M. & Rosner, M.R. (2002). ERK8, a new member of the mitogen-activated protein kinase family. J Biol Chem 277(19), 1673316743.
Ai, J.S., Wang, Q., Li, M., Shi, L.H., Ola, S.I., Xiong, B., Yin, S., Chen, D.Y. & Sun, Q.Y. (2008a). Roles of microtubules and microfilaments in spindle movements during rat oocyte meiosis. J Reprod Dev 54(5), 391396.
Ai, J.S., Wang, Q., Yin, S., Shi, L.H., Xiong, B., OuYang, Y.C., Hou, Y., Chen, D.Y., Schatten, H. & Sun, Q.Y. (2008b). Regulation of peripheral spindle movement and spindle rotation during mouse oocyte meiosis: New perspectives. Microsc Microanal 14(4), 349356.
Basto, R., Lau, J., Vinogradova, T., Gardiol, A., Woods, C.G., Khodjakov, A. & Raff, J.W. (2006). Flies without centrioles. Cell 125(7), 13751386.
Bogoyevitch, M.A. & Court, N.W. (2004). Counting on mitogen-activated protein kinases—ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 16(12), 13451354.
Chen, L., Chao, S.B., Wang, Z.B., Qi, S.T., Zhu, X.L., Yang, S.W., Yang, C.R., Zhang, Q.H., Ouyang, Y.C., Hou, Y., Schatten, H. & Sun, Q.Y. (2012). Checkpoint kinase 1 is essential for meiotic cell cycle regulation in mouse oocytes. Cell Cycle 11(10), 19481955.
Compton, D.A. (2000). Spindle assembly in animal cells. Annu Rev Biochem 69, 95114.
Fant, X., Merdes, A. & Haren, L. (2004). Cell and molecular biology of spindle poles and NuMA. Int Rev Cytol 238, 157.
Groehler, A.L. & Lannigan, D.A. (2010). A chromatin-bound kinase, ERK8, protects genomic integrity by inhibiting HDM2-mediated degradation of the DNA clamp PCNA. J Cell Biol 190(4), 575586.
Haren, L., Remy, M.H., Bazin, I., Callebaut, I., Wright, M. & Merdes, A. (2006). NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. J Cell Biol 172(4), 505515.
Huang, X., Tong, J.S., Wang, Z.B., Yang, C.R., Qi, S.T., Guo, L., Ouyang, Y.C., Quan, S., Sun, Q.Y., Qi, Z.Q., Huang, R.X. & Wang, H.L. (2011). JNK2 participates in spindle assembly during mouse oocyte meiotic maturation. Microsc Microanal 17(2), 197205.
Iavarone, C., Acunzo, M., Carlomagno, F., Catania, A., Melillo, R.M., Carlomagno, S.M., Santoro, M. & Chiariello, M. (2006). Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene. J Biol Chem 281(15), 1056710576.
Lewis, T.S., Shapiro, P.S. & Ahn, N.G. (1998). Signal transduction through MAP kinase cascades. Adv Cancer Res 74, 49139.
Li, M., Ai, J.S., Xu, B.Z., Xiong, B., Yin, S., Lin, S.L., Hou, Y., Chen, D.Y., Schatten, H. & Sun, Q.Y. (2008). Testosterone potentially triggers meiotic resumption by activation of intraoocyte SRC and MAPK in porcine oocytes. Biol Reprod 79(5), 897905.
Liu, H.C., Tang, Y., He, Z. & Rosenwaks, Z. (2010). Dicer is a key player in oocyte maturation. J Assist Reprod Genet 27, 571580.
Ma, W., Baumann, C. & Viveiros, M.M. (2010). NEDD1 is crucial for meiotic spindle stability and accurate chromosome segregation in mammalian oocytes. Dev Biol 339(2), 439450.
Mackey, Z.B., Koupparis, K., Nishino, M. & McKerrow, J.H. (2011). High-throughput analysis of an RNAi library identifies novel kinase targets in Trypanosoma brucei. Chem Biol Drug Des 78(3), 454463.
Pearson, G., Robinson, F., Beers Gibson, T., Xu, B.E., Karandikar, M., Berman, K. & Cobb, M.H. (2001). Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr Rev 22(2), 153183.
Quimby, B.B. & Dasso, M. (2003). The small GTPase Ran: Interpreting the signs. Curr Opin Cell Biol 15(3), 338344.
Robinson, M.J. & Cobb, M.H. (1997). Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9(2), 180186.
Schatten, H. (2008). The mammalian centrosome and its functional significance. Histochem Cell Biol 129(6), 667686.
Schatten, H. & Sun, Q.Y. (2011a). Centrosome dynamics during mammalian oocyte maturation with a focus on meiotic spindle formation. Mol Reprod Dev 78(10-11), 757768.
Schatten, H. & Sun, Q.Y. (2011b). The significant role of centrosomes in stem cell division and differentiation. Microsc Microanal 17(4), 506512.
Schuh, M. & Ellenberg, J. (2007). Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130(3), 484498.
Sun, S.C., Zhang, D.X., Lee, S.E., Xu, Y.N. & Kim, N.H. (2011). Ndc80 regulates meiotic spindle organization, chromosome alignment, and cell cycle progression in mouse oocytes. Microsc Microanal 17(3), 431439.
Tong, C., Fan, H.Y., Lian, L., Li, S.W., Chen, D.Y., Schatten, H. & Sun, Q.Y. (2002). Polo-like kinase-1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biol Reprod 67(2), 546554.
Verlhac, M.H., de Pennart, H., Maro, B., Cobb, M.H. & Clarke, H.J. (1993). MAP kinase becomes stably activated at metaphase and is associated with microtubule-organizing centers during meiotic maturation of mouse oocytes. Dev Biol 158(2), 330340.
Wadsworth, P., Lee, W.L., Murata, T. & Baskin, T.I. (2011). Variations on theme: Spindle assembly in diverse cells. Protoplasma 248(3), 439446.
Walczak, C.E. & Heald, R. (2008). Mechanisms of mitotic spindle assembly and function. Int Rev Cytol 265, 111158.
Wang, Q., Racowsky, C. & Deng, M. (2011). Mechanism of the chromosome-induced polar body extrusion in mouse eggs. Cell Div 6, 17.
Wang, R., He, G., Nelman-Gonzalez, M., Ashorn, C.L., Gallick, G.E., Stukenberg, P.T., Kirschner, M.W. & Kuang, J. (2007). Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition. Cell 128(6), 11191132.
Waskiewicz, A.J. & Cooper, J.A. (1995). Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin Cell Biol 7(6), 798805.
Xiong, B., Li, S., Ai, J.S., Yin, S., Ouyang, Y.C., Sun, S.C., Chen, D.Y. & Sun, Q.Y. (2008). BRCA1 is required for meiotic spindle assembly and spindle assembly checkpoint activation in mouse oocytes. Biol Reprod 79(4), 718726.
Xu, Y.M., Zhu, F., Cho, Y.Y., Carper, A., Peng, C., Zheng, D., Yao, K., Lau, A.T., Zykova, T.A., Kim, H.G., Bode, A.M. & Dong, Z. (2010). Extracellular signal-regulated kinase 8-mediated c-Jun phosphorylation increases tumorigenesis of human colon cancer. Cancer Res 70(8), 32183227.
Yao, L.J., Zhong, Z.S., Zhang, L.S., Chen, D.Y., Schatten, H. & Sun, Q.Y. (2004). Aurora-A is a critical regulator of microtubule assembly and nuclear activity in mouse oocytes, fertilized eggs, and early embryos. Biol Reprod 70(5), 13921399.
Yuan, J., Li, M., Wei, L., Yin, S., Xiong, B., Li, S., Lin, S.L., Schatten, H. & Sun, Q.Y. (2009). Astrin regulates meiotic spindle organization, spindle pole tethering and cell cycle progression in mouse oocytes. Cell Cycle 8(20), 33843395.
Yuan, J., Xu, B.Z., Qi, S.T., Tong, J.S., Wei, L., Li, M., Ouyang, Y.C., Hou, Y., Schatten, H. & Sun, Q.Y. (2010). MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment. PLoS One 5(6), e11247.
Zheng, K.G., Meng, X.Q., Yang, Y., Yu, Y.S., Liu, D.C. & Li, Y.L. (2007). Requirements of Src family kinase during meiotic maturation in mouse oocyte. Mol Reprod Dev 74(1), 125130.
Zhu, J., Qi, S.T., Wang, Y.P., Wang, Z.B., Ouyang, Y.C., Hou, Y., Schatten, H. & Sun, Q.Y. (2011). Septin1 is required for spindle assembly and chromosome congression in mouse oocytes. Dev Dyn 240(10), 22812289.


Related content

Powered by UNSILO

The Distribution and Possible Role of ERK8 in Mouse Oocyte Meiotic Maturation and Early Embryo Cleavage

  • Shang-Wu Yang (a1) (a2) (a3), Hao Huang (a3), Chen Gao (a4), Lei Chen (a2), Shu-Tao Qi (a2), Fei Lin (a2), Jian-Xin Wang (a5), Yi Hou (a2), Fu-Qi Xing (a1) and Qing-Yuan Sun (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.