Impaired mitotic progression and preimplantation lethality in mice lacking OMCG1, a new evolutionarily conserved nuclear protein.
While highly conserved through evolution, the cell cycle has been extensively modified to adapt to new developmental programs. Recently, analyses of mouse mutants revealed that several important cell cycle regulators are either dispensable for development or have a tissue- or cell-type-specific function, indicating that many aspects of cell cycle regulation during mammalian embryo development remain to be elucidated. Here, we report on the characterization of a new gene, Omcg1, which codes for a nuclear zinc finger protein. Embryos lacking Omcg1 die by the end of preimplantation development. In vitro cultured Omcg1-null blastocysts exhibit a dramatic reduction in the total cell number, a high mitotic index, and the presence of abnormal mitotic figures. Importantly, we found that Omcg1 disruption results in the lengthening of M phase rather than in a mitotic block. We show that the mitotic delay in Omcg1-/- embryos is associated with neither a dysfunction of the spindle checkpoint nor abnormal global histone modifications. Taken together, these results suggest that Omcg1 is an important regulator of the cell cycle in the preimplantation embryo.
Unité de Biologie du Développement, CNRS URA 2578, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Jérôme
J
Artus
Sandrine
S
Vandormael-Pournin
Morten
M
Frödin
Karim
K
Nacerddine
Charles
C
Babinet
Michel
M
Cohen-Tannoudji
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D017124:Conserved Sequence; D047108:Embryonic Development; D005260:Female; D015870:Gene Expression; D005804:Genes, Lethal / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D006657:Histones; D009687:Nuclear Proteins; C503327:OMCG1 protein, mouse