Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

Authors

  • Sharon Zins Rousso,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Rachel Ben-Haroush Schyr,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Michal Gur,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Noam Zouela,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Hadas Kot-Leibovich,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Yehuda Shabtai,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Natalia Koutsi-Urshanski,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Danila Baldessari,

    1. Division of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany
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  • Graciela Pillemer,

    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
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  • Christof Niehrs,

    1. Division of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany
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  • Abraham Fainsod

    Corresponding author
    1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel
    • Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, POB 12272, Jerusalem 91120, Israel
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Abstract

Gastrulation marks the onset of germ layer formation from undifferentiated precursor cells maintained by a network including the Pou5f1 gene, Oct3/4. Negative regulation of the undifferentiated state is a prerequisite for germ layer formation and subsequent development. A novel cross-regulatory network was characterized including the Pou5f1 and Cdx1 genes as part of the signals controlling the onset of gastrulation. Of particular interest was the observation that, preceding gastrulation, the Xenopus Oct3/4 factors, Oct60, Oct25, and Oct91, positively regulate Cdx1 expression through FGF signaling, and during gastrulation the Oct3/4 factors become repressors of Cdx1. Cdx1 negatively regulates the Pou5f1 genes during gastrulation, thus contributing to the repression of the network maintaining the undifferentiated state and promoting the onset of gastrulation. These regulatory interactions suggest that Oct3/4 initiates its own negative autoregulation through Cdx1 up-regulation to begin the repression of pluripotency in preparation for the onset of gastrulation and germ layer differentiation. Developmental Dynamics 240:796–807, 2011. © 2011 Wiley-Liss, Inc.

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