Most POU family transcription factors are temporally and spatially restricted during development and play pivotal roles in specific cell fate determination events. Oct1 (Pou2f1), however, is ubiquitously expressed in embryonic and adult mouse tissues; so, does Oct1 have a developmental role? On p. 3551, Fatima Cavaleri and colleagues report that Oct1 regulates trophoblast development during mouse embryogenesis. The researchers generate Oct1-null embryos and show that they fail to develop beyond the early primitive streak stage. Analysis of the mutant embryos reveals that they lack normal maternal-embryonic interfaces because of reduced extra-embryonic ectoderm (ExE) formation and the absence of the ectoplacental cone – two extra-embryonic tissues generated from the trophectoderm cells that overlie the inner cell mass (which forms the embryo). Other experiments indicate that Oct1 loss is incompatible with the derivation of trophoblast stem cells, which normally reside in the ExE. The researchers suggest, therefore, that Oct1 is primarily required for the maintenance and differentiation of the trophoblast stem cell compartment during early post-implantation development.