title: Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation.
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.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Sharon Zins
authors.initials: SZ
authors.lastname: Rousso
authors.forename: Rachel Ben-Haroush
authors.initials: RB
authors.lastname: Schyr
authors.forename: Michal
authors.initials: M
authors.lastname: Gur
authors.forename: Noam
authors.initials: N
authors.lastname: Zouela
authors.forename: Hadas
authors.initials: H
authors.lastname: Kot-Leibovich
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shabtai
authors.forename: Natalia
authors.initials: N
authors.lastname: Koutsi-Urshanski
authors.forename: Danila
authors.initials: D
authors.lastname: Baldessari
authors.forename: Graciela
authors.initials: G
authors.lastname: Pillemer
authors.forename: Christof
authors.initials: C
authors.lastname: Niehrs
authors.forename: Abraham
authors.initials: A
authors.lastname: Fainsod
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics; D046149:Embryo Culture Techniques; D004625:Embryo, Nonmammalian; D054262:Gastrulation / Q000235:genetics* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D029867:Xenopus Proteins; C000605378:cdx2 protein, Xenopus