Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Timeline
  • Published:

The elusive cytostatic factor in the animal egg

Nature Reviews Molecular Cell Biology volume 1, pages 228–231 (2000)Cite this article

Abstract

While animal eggs await fertilization, their cell cycle needs to be halted. The molecule responsible for this arrest ? the cytostatic factor ? was first described in 1971. But its identity was not revealed until 1989, and even now questions remain about this elusive factor.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Changes in activity of maturation-promoting factor and the cytostatic factor during oocyte maturation, fertilization and cleavage.
Figure 2: Blastomere of a Rana pipiens embryo injected with the cytostatic factor.
Figure 3: Progression of meiosis during oocyte maturation and the timing of fertilization.

References

  1. Lillie, F. R. Studies of fertilization in Nereis. I. The cortical changes in the egg: II. Partial fertilization. J. Morphol. 22, 361?393 (1911).

    Article  Google Scholar 

  2. Lillie, F. R. Studies of fertilization in Nereis. VI. The fertilizing power of porations of the spermatozoon. J. Exp. Zool. 12, 427 ?476 (1912).

    Article  Google Scholar 

  3. Boveri, T. Zellenstudien VI. Die Entwicklung dispermer Seeigeleier. Ein Beitrag zur Befruchtungslehre und zur Theorie des Kernes. Jena Zeitschri. Naturw. 43, 1?292 (1907).

    Google Scholar 

  4. Loeb, J. Artificial Parthenogenesis and Fertilization (Univ. Chicago Press, Chicago, 1913).

    Google Scholar 

  5. Masui, Y. in Biology of Fertilisation Vol 1 (eds Metz, C. B. & Monroy, A.) 189?219 (Academic, New York, 1985).

    Book  Google Scholar 

  6. Masui, Y. & Markert, C. L. Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J. Exp. Zool. 177, 129?145 ( 1971).

    Article  CAS  Google Scholar 

  7. Dettlaff, T. A., Nikitina, L. A. & Stroeva, O. G. The role of the germinal vesicle in oocyte maturataion in anurans as revealed by the removal and transplantation of nuclei. J. Embryol. Exp. Morphol. 12, 851? 873 (1964).

    CAS  PubMed  Google Scholar 

  8. Schuetz, A. W. Action of hormones on germinal vesicle breakdown in frog oocytes (Rana pipiens) in vitro. J. Exp. Zool. 166, 347?354 (1967).

    Article  CAS  Google Scholar 

  9. Masui, Y. Relative roles of pituitary, follicle cells, and progesterone in the induction of oocyte maturation of Rana pipiens. J. Exp. Zool. 166, 365?376 (1967).

    Article  CAS  Google Scholar 

  10. Masui, Y. The role of 'cytostatic factor (CSF)' in the control of oocyte cell cycles ? a summary of 20 years of study. Dev. Growth Differ. 33, 542?551 (1991).

    Article  Google Scholar 

  11. Masui, Y. A cytostatic factor in amphibian oocytes: its extraction and partial characterization . J. Exp. Zool. 187, 141? 147 (1974).

    Article  CAS  Google Scholar 

  12. Meyerhof, P. G. & Masui, Y. Ca and Mg control of cytoplasmic factors from Rana pipiens oocytes which cause metaphase and cleavage arrest. Dev. Biol. 61, 214? 229 (1977).

    Article  CAS  Google Scholar 

  13. Shibuya, E. K. & Masui, Y. Stabilization and enhancement of primary cytostatic factor (CSF) by ATP and NaF in amphibian egg cytosols. Dev. Biol. 129, 253? 265 (1988).

    Article  CAS  Google Scholar 

  14. Shibuya, E. K. & Masui, Y. Molecular characteristics of cytostatic factors in amphibian egg cytosols. Development 106, 799?808 (1989).

    CAS  PubMed  Google Scholar 

  15. Sagata, N., Watanaabe, N., Vande Woude, G. F. & Ikawa, Y. The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs. Nature 342, 512?518 (1989).

    Article  CAS  Google Scholar 

  16. Tachibana, K., Tanaka, D., Isobe, T. & Kishimoto, T. c?Mos forces the mitotic cell cycle to undergo meiosis II to produce haploid gametes . Proc. Natl Acad. Sci. USA (in the press).

  17. Mazia, D. The release of calcium in Arbacia eggs on fertilisation. J. Cell. Comp. Physiol. 10, 291?304 (1937).

    Article  CAS  Google Scholar 

  18. Steinhardt, R. A., Epel, D., Carroll, E. J. & Yanagimachi, R. Is calcium ionophore a universal activator for unfertilized eggs? Nature 252, 41?43 (1974).

    Article  CAS  Google Scholar 

  19. Ridgeway, E. B., Gilkey, J. C. & Jaffe, L. F. Free calcium increases explosively in activating medaka eggs. Proc. Natl Acad. Sci. USA 74, 623?627 (1977).

    Article  Google Scholar 

  20. Watanabe, N., Vande Woude, G. F., Ikawa, Y. & Sagata, N. Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs. Nature 342 , 505?511 (1989).

    Article  CAS  Google Scholar 

  21. Lorca, T. et al. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 366, 270?273 ( 1993).

    Article  CAS  Google Scholar 

  22. Zampetti-Bosseler, F., Huez, G. & Brachet, J. Effects of several inhibitors of macromolecular synthesis upon maturation of marine invertebrate oocytes. Exp. Cell Res. 78, 383?393 ( 1973).

    Article  CAS  Google Scholar 

  23. Neant, I. & Guerrier, P. Meiosis reinitiation in the mollusc, Patella vulgata: regulation of MPF, CSF and chromosome condensation activity by intracellular pH, protein synthesis and phosphorylation. Development 102, 505?516 ( 1988).

    CAS  Google Scholar 

  24. Siracusa, G., Whittingham, D. G., Molinaro, M. & Vivarelli, E. Parthenogenetic activation of mouse oocytes induced by inhibitors of protein synthesis. J. Embryol. Exp. Morph. 43, 157 ?166 (1978).

    CAS  PubMed  Google Scholar 

  25. Iwao, Y. & Masui, Y. Activation of newt eggs in the absence of Ca2+ activity by treatment with cycloheximide or D 2O. Dev. Growth Differ. 37, 641? 651 (1995).

    Article  CAS  Google Scholar 

  26. Zhang, S. C. & Masui, Y. Activation of Xenopus laevis eggs in the absence of intracellular Ca activity by the protein phosphorylation inhibitor, 6-dimethylaminopurine (6-DMAP). J. Exp. Zool. 262, 317?329 (1992).

    Article  CAS  Google Scholar 

  27. Rime, H., Neant, I., Guerrier, P. & Ozon, R. 6-Dimethylaminopurine (6-DMAP), a reversible inhibitor of the transition to metaphase during the first meiotic cell division of the mouse oocyte. Dev. Biol. 133, 169?179 (1989).

    Article  CAS  Google Scholar 

  28. Bodart, J.-F. et al. Activation of Xenopus eggs by the kinase inhibitor 6-DMAP suggests a differential regulation of cyclin B and p39mos proteolysis . Exp. Cell Res. 253, 413? 421 (1999).

    Article  CAS  Google Scholar 

  29. Gross, P., Spindle, W. & Cousineau, G. H. Decoupling of protein and RNA synthesis during deuterium parthenogenesis in sea urchin eggs. Biochem. Biophys. Res. Comm. 13, 405?410 ( 1963).

    Article  CAS  Google Scholar 

  30. Kubiak, J. Z., Weber, M., de Pennart, H., Winston, N. J. & Maro, B. The metaphase II arrest in mouse oocytes is controlled through microtubule-dependent destruction of cyclin B in the presence of CSF. EMBO J. 12, 3773? 3778 (1993).

    Article  CAS  Google Scholar 

  31. Moses, R. M., Kline, D. & Masui, Y. Maintenance of metaphase in colcemid-treated mouse eggs by distinct calcium- and 6-dimethylaminopurine (6-DMAP)-sensitive mechanisms . Dev. Biol. 167, 329?337 (1995).

    Article  CAS  Google Scholar 

  32. Sagata, N. What does Mos do in oocytes and somatic cells? BioEssays 19, 13?21 (1997).

    Article  CAS  Google Scholar 

  33. Haccard, O. et al. Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase. Science 262, 1262? 1265 (1993).

    Article  CAS  Google Scholar 

  34. Verlhac, M.-H. et al. Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse. Development 122, 815?822 (1996).

    CAS  PubMed  Google Scholar 

  35. Colledge, W. H., Carlton, M. B. L., Udy, G. B. & Evans, M. J. Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs. Nature 370, 65? 67 (1994).

    Article  CAS  Google Scholar 

  36. Hashimoto, N. et al. Parthenogenetic activation of oocytes in c-mos-deficient mice. Nature 370, 68?71 (1994).

    Article  CAS  Google Scholar 

  37. Bhatt, R. R. & Ferrell, J. E. Jr The protein kinase p90 Rsk as an essential mediator of cytostatic factor activity. Science 286, 1362?1365 ( 1999).

    Article  CAS  Google Scholar 

  38. Gross, S. D., Schwab, M. S., Lewellyn, A. L. & Maller, J. L. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science 286, 1365? 1367 (1999).

    Article  CAS  Google Scholar 

  39. Gross, S. D. et al. The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90Rsk. Curr. Biol. 10, 430?438 (2000).

    Article  CAS  Google Scholar 

  40. Chau, A. S. S. & Shibuya, E. K. Mos-induced p42 mitogen-activated protein kinase activation stabilizes M-phase in Xenopus egg extracts after cyclin destruction. Biol. Cell 90, 565?572 (1998).

    Article  CAS  Google Scholar 

  41. Guadagno, T. M. & Ferrell, J. E. Jr Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts. Science 282, 13? 21 (1997).

    Google Scholar 

  42. Zecevic, M. et al. Active MAP kinase in mitosis: localization at kinetochores and association with motor protein CENP-E. J. Cell Biol. 142, 1547?1558 (1998).

    Article  CAS  Google Scholar 

  43. Duesbery, N. S. et al. CNEP-E is an essential kinetochore motor in maturing oocytes and is masked during Mos-dependent, cell cycle arrest at metaphase. Proc. Natl Acad. Sci. USA 94, 9165? 9170 (1997).

    Article  CAS  Google Scholar 

  44. Lohka, M. J., Hayes, M. K. & Maller, J. L. Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc. Natl Acad. Sci. USA 85, 3009?3013 (1988).

    Article  CAS  Google Scholar 

  45. Pelec, S. L., Tombes, R. M., Meijer, L. & Krebs, E. G. Activation of myelin protein during echinoderm oocyte maturation and egg fertilization . Dev. Biol. 130, 28?36 (1988).

    Article  Google Scholar 

  46. Russo, G. L., Kyozuka, K., Antonazzo, L., Tosti, E. & Dale, B. Maturation promoting factor in ascidian oocytes is regulated by different intracellular signasls at meiosis I and II. Development 122, 1995? 2003 (1996).

    CAS  PubMed  Google Scholar 

  47. Tachibana, K., Machida, T., Nomura, Y. & Kishimoto, T. MAP kinase links the fertilization signal transduction pathwayto the G1/S-phase in starfish eggs. EMBO J. 16, 4333? 4339 (1997).

    Article  CAS  Google Scholar 

  48. Fisher, D. et al. MAP kinase inactivation is required only for G2?M phase transition in early embryogenesis cell cycles of the starfish Marthasterias glacilis and Astropecten aranciacus. Dev. Biol. 202, 1?13 (1998).

    Article  CAS  Google Scholar 

  49. Bitangol, J. C. et al. Activation of the p42MAPK pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts. Mol. Biol. Cell 9, 451?467 (1998).

    Article  Google Scholar 

Download references

Acknowledgements

I thank Stacey Hayden for her assistance in preparing and reading the manuscript.

Author information

Authors and Affiliations

  1. the Department of Zoology, University of Toronto, 25 Harbord Street, Toronto, M5S 3G5, Ontario, Canada

    Yoshio Masui

Authors
  1. Yoshio Masui
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASE LINKS

Mos

CaMKII

MAPKs

cdc27

CENPE

Rights and permissions

Reprints and permissions

About this article

Cite this article

Masui, Y. The elusive cytostatic factor in the animal egg . Nat Rev Mol Cell Biol 1, 228–231 (2000). https://doi.org/10.1038/35043096

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35043096

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing