title: Oct1 regulates trophoblast development during early mouse embryogenesis.
abstract: Oct1 (Pou2f1) is a transcription factor of the POU-homeodomain family that is unique in being ubiquitously expressed in both embryonic and adult mouse tissues. Although its expression profile suggests a crucial role in multiple regions of the developing organism, the only essential function demonstrated so far has been the regulation of cellular response to oxidative and metabolic stress. Here, we describe a loss-of-function mouse model for Oct1 that causes early embryonic lethality, with Oct1-null embryos failing to develop beyond the early streak stage. Molecular and morphological analyses of Oct1 mutant embryos revealed a failure in the establishment of a normal maternal-embryonic interface due to reduced extra-embryonic ectoderm formation and lack of the ectoplacental cone. Oct1(-/-) blastocysts display proper segregation of trophectoderm and inner cell mass lineages. However, Oct1 loss is not compatible with trophoblast stem cell derivation. Importantly, the early gastrulation defect caused by Oct1 disruption can be rescued in a tetraploid complementation assay. Oct1 is therefore primarily required for the maintenance and differentiation of the trophoblast stem cell compartment during early post-implantation development. We present evidence that Cdx2, which is expressed at high levels in trophoblast stem cells, is a direct transcriptional target of Oct1. Our data also suggest that Oct1 is required in the embryo proper from late gastrulation stages onwards.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgenstrasse, 20 48149 Münster, Germany.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sebastiano
authors.forename: Mathieu
authors.initials: M
authors.lastname: Dalvai
authors.forename: Luca
authors.initials: L
authors.lastname: Gentile
authors.forename: Karin
authors.initials: K
authors.lastname: Schubart
authors.forename: Julien
authors.initials: J
authors.lastname: Sutter
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Wu
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.forename: Daniel
authors.initials: D
authors.lastname: Esch
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Ju
authors.forename: Karin
authors.initials: K
authors.lastname: Hübner
authors.forename: Marcos Jesus Arauzo
authors.initials: MJ
authors.lastname: Bravo
authors.forename: Hans Robert
authors.initials: HR
authors.lastname: Schöler
authors.forename: Fatima
authors.initials: F
authors.lastname: Cavaleri
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D020964:Embryo Loss / Q000235:genetics; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005865:Gestational Age; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology*
chemical_list: D027702:Organic Cation Transporter 1