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The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes

The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes
The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes
FZR1, an activator of the anaphase-promoting complex/cyclosome (APC/C), is recognized for its roles in the mitotic cell cycle. To examine its meiotic function in females we generated an oocyte-specific knockout of the Fzr1 gene (Fzr1(?/?)). The total number of fully grown oocytes enclosed in cumulus complexes was 35-40% lower in oocytes from Fzr1(?/?) mice and there was a commensurate rise in denuded, meiotically advanced and/or fragmented oocytes. The ability of Fzr1(?/?) oocytes to remain prophase I/germinal vesicle (GV) arrested in vitro was also compromised, despite the addition of the phosphodiesterase milrinone. Meiotic competency of smaller diameter oocytes was also accelerated by Fzr1 loss. Cyclin B1 levels were elevated ~5-fold in Fzr1(?/?) oocytes, whereas securin and CDC25B, two other APC/C(FZR1) substrates, were unchanged. Cyclin B1 overexpression can mimic the effects of Fzr1 loss on GV arrest and here we show that cyclin B1 knockdown in Fzr1(?/?) oocytes affects the timing of meiotic resumption. Therefore, the effects of Fzr1 loss are mediated, at least in part, by raised cyclin B1. Thus, APC/C(FZR1) activity is required to repress cyclin B1 levels in oocytes during prophase I arrest in the ovary, thereby maintaining meiotic quiescence until hormonal cues trigger resumption.
1477-9129
905-913
Holt, JE
c2b8b241-75af-4c44-972b-af9508fcfc2a
Tran, SMT
802c42ac-f232-4797-be29-1e580605d63a
Stewart, JL
7b53fa1e-8708-4777-bf1f-6833437f5eaa
Minahan, K
f611d3dd-baba-413e-ba1c-2511f2f3d90a
García-Higuera, I
a624ede1-2ccb-4256-a4cc-f068a51a1d0f
Moreno, S
3b8cac11-c963-4222-befd-162ee0587ac2
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Holt, JE
c2b8b241-75af-4c44-972b-af9508fcfc2a
Tran, SMT
802c42ac-f232-4797-be29-1e580605d63a
Stewart, JL
7b53fa1e-8708-4777-bf1f-6833437f5eaa
Minahan, K
f611d3dd-baba-413e-ba1c-2511f2f3d90a
García-Higuera, I
a624ede1-2ccb-4256-a4cc-f068a51a1d0f
Moreno, S
3b8cac11-c963-4222-befd-162ee0587ac2
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Holt, JE, Tran, SMT, Stewart, JL, Minahan, K, García-Higuera, I, Moreno, S and Jones, KT (2011) The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes. Development, 138 (5), 905-913. (doi:10.1242/dev.059022). (PMID:21270054)

Record type: Article

Abstract

FZR1, an activator of the anaphase-promoting complex/cyclosome (APC/C), is recognized for its roles in the mitotic cell cycle. To examine its meiotic function in females we generated an oocyte-specific knockout of the Fzr1 gene (Fzr1(?/?)). The total number of fully grown oocytes enclosed in cumulus complexes was 35-40% lower in oocytes from Fzr1(?/?) mice and there was a commensurate rise in denuded, meiotically advanced and/or fragmented oocytes. The ability of Fzr1(?/?) oocytes to remain prophase I/germinal vesicle (GV) arrested in vitro was also compromised, despite the addition of the phosphodiesterase milrinone. Meiotic competency of smaller diameter oocytes was also accelerated by Fzr1 loss. Cyclin B1 levels were elevated ~5-fold in Fzr1(?/?) oocytes, whereas securin and CDC25B, two other APC/C(FZR1) substrates, were unchanged. Cyclin B1 overexpression can mimic the effects of Fzr1 loss on GV arrest and here we show that cyclin B1 knockdown in Fzr1(?/?) oocytes affects the timing of meiotic resumption. Therefore, the effects of Fzr1 loss are mediated, at least in part, by raised cyclin B1. Thus, APC/C(FZR1) activity is required to repress cyclin B1 levels in oocytes during prophase I arrest in the ovary, thereby maintaining meiotic quiescence until hormonal cues trigger resumption.

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More information

e-pub ahead of print date: 26 January 2011
Published date: March 2011
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 340337
URI: http://eprints.soton.ac.uk/id/eprint/340337
ISSN: 1477-9129
PURE UUID: 2693e19b-c9a5-4540-92e6-f5ab6fb68584
ORCID for KT Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 19 Jun 2012 12:10
Last modified: 05 Nov 2019 01:38

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