Trophectoderm Lineage Determination in Cattle

SummaryThe trophectoderm (TE) and inner cell mass (ICM) are committed and marked by reciprocal expression of Cdx2 and Oct4 in mouse late blastocysts. We find that the TE is not committed at equivalent stages in cattle, and that bovine Cdx2 is required later, for TE maintenance, but does not repress Oct4 expression. A mouse Oct4 (mOct4) reporter, repressed in mouse TE, remained active in the cattle TE; bovine Oct4 constructs were not repressed in the mouse TE. mOct4 has acquired Tcfap2 binding sites mediating Cdx2-independent repression—cattle, humans, and rabbits do not contain these sites and maintain high Oct4 levels in the TE. Our data suggest that the regulatory circuitry determining ICM/TE identity has been rewired in mice, to allow rapid TE differentiation and early blastocyst implantation. These findings thus emphasize ways in which mice may not be representative of the earliest stages of mammalian development and stem cell biology.

Graphical AbstractFigure optionsDownload high-quality image (187 K)Download as PowerPoint slideHighlights
► Late blastocyst cattle trophectoderm (TE) expresses Oct4 and is not yet committed
► Cdx2 is required for cattle TE maintenance but not for Oct4 repression
► The mouse Oct4 locus is also repressed via AP2 binding sites that are not conserved
► TE regulatory circuitry correlates with the timing of TE commitment and implantation