Distinct roles for the mammalian A-type cyclins during oogenesis.
There are two A-type cyclins in higher vertebrates, cyclin A1 and A2. Targeted mutagenesis has shown that cyclin A2 is essential for early embryonic development while cyclin A1 is required only for male meiosis. The embryonic lethality of cyclin A2 knockout mice has obviated understanding its role in other aspects of mammalian development, including the germ line. We reported previously that cyclin A2 expression in the male germ line is consistent with a role in both mitotic and meiotic cell cycles. Using in situ hybridization and immunohistochemistry, we now observe high levels of cyclin A2 in granulosa cells and less-abundant but readily detectable expression in ovarian and ovulated oocytes. A decrease in cyclin A2 protein was observed in oocytes from embryonic stages to post-natal and adult ovaries. Interestingly, cyclin A2 protein was nuclear in oocytes from embryonic day 13.5 to 15.5, changing to largely cytoplasmic in oocytes from embryonic day 16.5 to post-natal and adults. Readily detectable expression of the cyclin-dependent kinases Cdk1 and Cdk2, two common partners for the A-type cyclins, was observed in granulosa cells and oocytes at all stages of folliculogenesis. Cdk1 was predominantly cytoplasmic, whereas Cdk2 was both cytoplasmic and nuclear in oocytes. No cyclin A1 expression, at either the mRNA level or the protein level was detected in either embryonic or adult ovaries, consistent with the full fertility observed in female cyclin A1-deficient mice. These results suggest that in the female germ line, cyclin A2 but not cyclin A1 has distinct roles in both mitosis and meiosis.
Persson
Jenny Liao
JL
Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA.
Zhang
Qi
Q
Wang
Xiang Yuan
XY
Ravnik
Stuart E
SE
Muhlrad
Samantha
S
Wolgemuth
Debra J
DJ
D000818:Animals; D016203:CDC2 Protein Kinase / Q000032:analysis; D002467:Cell Nucleus / Q000737:chemistry; D019925:Cyclin A / Q000032:analysis* / Q000235:genetics; D056751:Cyclin A2; D051357:Cyclin-Dependent Kinase 2 / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006107:Granulosa Cells / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D009865:Oocytes / Q000737:chemistry*; D009866:Oogenesis / Q000502:physiology*; D010060:Ovulation / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis
C508184:CCNA2 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2; D012333:RNA, Messenger; D016203:CDC2 Protein Kinase; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2