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Published online December 26, 2006
doi:10.1083/jcb.200607070
The Journal of Cell Biology, Vol. 176, No. 1, 65-75
The Rockefeller University Press, 0021-9525 $30.00
© 2006 Marangos et al.
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Article

Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APCCdh1



Petros Marangos1, Emmy W. Verschuren2, Ruby Chen3, Peter K. Jackson2, and John Carroll1

1 Department of Physiology, University College London, London WC1E 6BT, England, UK
2 Department of Pathology, School of Medicine, and 3 Department of Obstetrics and Gynecology, Division of Reproductive Biology, Stanford University, Palo Alto, CA 94305

Correspondence to Petros Marangos: p.marangos{at}ucl.ac.uk; or John Carroll: j.carroll{at}ucl.ac.uk

Mammalian oocytes are arrested in prophase of the first meiotic division. Progression into the first meiotic division is driven by an increase in the activity of maturation-promoting factor (MPF). In mouse oocytes, we find that early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex (APC) that is responsible for cyclin B destruction and inactivation of MPF, is present at prophase I and undergoes Skp1–Cul1–F-box/ßTrCP-mediated destruction immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the inhibition of Emi1 destruction in prophase-arrested oocytes leads to a stabilization of cyclin B1–GFP that is sufficient to trigger GVBD. In contrast, the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1–GFP destruction, resulting in an attenuation of MPF activation and a delay of entry into the first meiotic division. Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APCCdh1.

Abbreviations used in this paper: APC, anaphase-promoting complex; cRNA, complementary RNA; CSF, cytostatic factor; Emi1, early mitotic inhibitor 1; GV, germinal vesicle; GVBD, GV breakdown; hCG, human chorionic gonadotrophin; IBMX, 3-isobutyl-1-methylxanthine; MBP, myelin basic protein; MO, morpholino; MPF, maturation-promoting factor; PMSG, pregnant male serum gonadotrophin; PVA, polyvinyl alcohol; SCF, Skp1–Cul1–F box.


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