Oct1 regulates trophoblast development during early mouse embryogenesis.
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.
Sebastiano
Vittorio
V
Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgenstrasse, 20 48149 Münster, Germany.
Dalvai
Mathieu
M
Gentile
Luca
L
Schubart
Karin
K
Sutter
Julien
J
Wu
Guang-Ming
GM
Tapia
Natalia
N
Esch
Daniel
D
Ju
Jin-Young
JY
Hübner
Karin
K
Bravo
Marcos Jesus Arauzo
MJ
Schöler
Hans Robert
HR
Cavaleri
Fatima
F
Matthias
Patrick
P
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*
D027702:Organic Cation Transporter 1