Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development.
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.
Gonzalez
Michael A
MA
Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, UK. mg322@hutchison-mrc.cam.ac.uk
Tachibana
Kiku-e K
KE
Adams
David J
DJ
van der Weyden
Louise
L
Hemberger
Myriam
M
Coleman
Nicholas
N
Bradley
Allan
A
Laskey
Ronald A
RA
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development; D064248:Geminin; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008322:Mammals / Q000196:embryology*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D061988:Proteasome Inhibitors; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology
D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C493965:Cdkn1c protein, mouse; C487514:Cdx2 protein, mouse; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D064248:Geminin; C577997:Gmnn protein, mouse; D018398:Homeodomain Proteins; D007976:Leupeptins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D061988:Proteasome Inhibitors; D014157:Transcription Factors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde