Oct4 Cell-Autonomously Promotes Primitive Endoderm Development in the Mouse Blastocyst

• Maternal Oct4 is dispensable for development
• Oct4 promotes primitive endoderm and represses trophectoderm fates in parallel
• Oct4 acts upstream of Fgf4 in epiblast and downstream of Mapk in primitive endoderm
• Oct4 is required for expression of metabolic pathway genes in the blastocyst

SummaryIn embryonic stem (ES) cells and in early mouse embryos, the transcription factor Oct4 is an essential regulator of pluripotency. Oct4 transcriptional targets have been described in ES cell lines; however, the molecular mechanisms by which Oct4 regulates establishment of pluripotency in the epiblast (EPI) have not been fully elucidated. Here, we show that neither maternal nor zygotic Oct4 is required for the formation of EPI cells in the blastocyst. Rather, Oct4 is first required for development of the primitive endoderm (PE), an extraembryonic lineage. EPI cells promote PE fate in neighboring cells by secreting Fgf4, and Oct4 is required for expression of Fgf4, but we show that Oct4 promotes PE development cell-autonomously, downstream of Fgf4 and Mapk. Finally, we show that Oct4 is required for the expression of multiple EPI and PE genes as well as multiple metabolic pathways essential for the continued growth of the preimplantation embryo.

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