title: Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development.
abstract: 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.
authors.affiliation: Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, UK. mg322@hutchison-mrc.cam.ac.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gonzalez
authors.forename: Kiku-e K
authors.initials: KE
authors.lastname: Tachibana
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weyden
authors.forename: Myriam
authors.initials: M
authors.lastname: Hemberger
authors.forename: Nicholas
authors.initials: N
authors.lastname: Coleman
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Laskey
mesh_terms: 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
chemical_list: 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