Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development

被引:103
作者
Gonzalez, Michael A. [1 ]
Tachibana, Kiku-e K.
Adams, David J.
van der Weyden, Louise
Hemberger, Myriam
Coleman, Nicholas
Bradley, Allan
Laskey, Ronald A.
机构
[1] MRC, Canc Cell Unit, Hutchison MRC Res Ctr, Cambridge CB2 2XZ, England
[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
[3] Babraham Inst, Cambridge CB2 4AT, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
geminin; endoreduplication; trophoblast; Oct4; Cdx2; pluripotency;
D O I
10.1101/gad.379706
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In multicellular eukaryotes, geminin prevents overreplication of DNA in proliferating cells. Here, we show that genetic ablation of geminin in the mouse prevents formation of inner cell mass (ICM) and causes premature endoreduplication at eight cells, rather than 32 cells. All cells in geminin-deficient embryos commit to the trophoblast cell lineage and consist of trophoblast giant cells (TGCs) only. Geminin is also down-regulated in TGCs of wild-type blastocysts during S and gap-like phases by proteasome-mediated degradation, suggesting that loss of geminin is part of the mechanism regulating endoreduplication.
引用
收藏
页码:1880 / 1884
页数:5
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