Direct repression of <i>Nanog</i> and <i>Oct4</i> by OTX2 modulates the contribution of epiblast-derived cells to germline and somatic lineage

ABSTRACT In mammals, the pre-gastrula proximal epiblast gives rise to primordial germ cells (PGCs) or somatic precursors in response BMP4 and WNT signaling. Entry into germline requires activation of a naïve-like pluripotency gene regulatory network (GRN). Recent work has shown that suppression OTX2 expression by allows develop PGC fate precise temporal window. However, mechanisms which suppresses are unknown. Here, we show that, mice, prevents from activating GRN direct repression Oct4 Nanog. Loss this control during differentiation vitro causes widespread deregulated LIF, These abnormalities, specific cell culture conditions, result massive entry at expense mesoderm differentiation. Increased generation PGCs also occurs mutant embryos. We propose OTX2-mediated repressive Nanog is basis mechanism determines contribution lineage.