Oct-4: Gatekeeper in the Beginnings of Mammalian Development


  • Maurizio Pesce,

    1. Laboratorio di Patologia Vascolare, Istituto Dermopatico dell' Immacolata, Rome, Italy
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  • Hans R. Schöler Ph.D.

    Corresponding author
    1. Center for Animal Transgenesis and Germ Cell Research, Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA
    • Director, Center for Animal Transgenesis and Germ Cell Research, Germline Development Group, New Bolton Center, 382 W. Street Rd., Kennett Square, Pennsylvania 19348, USA. Telephone: 610-444-5800×2289; Fax: 610-925-8121
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The Oct-4 POU transcription factor is expressed in mouse totipotent embryonic stem and germ cells. Differentiation of totipotent cells to somatic lineages occurs at the blastocyst stage and during gastrulation, simultaneously with Oct-4 downregulation. Stem cell lines derived from the inner cell mass and the epiblast of the mouse embryo express Oct-4 only if undifferentiated. When embryonic stem cells are triggered to differentiate, Oct-4 is downregulated thus providing a model for the early events linked to somatic differentiation in the developing embryo. In vivo mutagenesis has shown that loss of Oct-4 at the blastocyst stage causes the cells of the inner cell mass to differentiate into trophectoderm cells. Recent experiments indicate that an Oct-4 expression level of roughly 50%-150% of the endogenous amount in embryonic stem cells is permissive for self-renewal and maintenance of totipotency. However, upregulation above these levels causes stem cells to express genes involved in the lineage differentiation of primitive endoderm. These novel advances along with latest findings on Oct-4-associated factors, target genes, and dimerization ability, provide new insights into the understanding of the early steps regulating mammalian embryogenesis.