Oct4: an orchestrator of early development Free

The transcription factor Oct4 is known for its role in regulating cell fate decisions in the preimplantation embryo, and for maintaining pluripotency in embryonic stem cells. However, although Oct4 expression is known to persist in the epiblast of postimplantation mouse embryos, its role in later stages of development is less clear. Here, Jenny Nichols and colleagues use a conditional genetic model to delete Oct4 from epiblast cells soon after implantation and reveal unexpected developmental roles for Oct4. They first demonstrate that Oct4 deletion during the onset of gastrulation results in disorganisation of the epiblast and a cell-autonomous increase in Nanog expression. Surprisingly, however, Oct4 loss also disrupts axial organisation of the embryo; the AVE (a population of cells that helps specify the anterior-posterior axis) is positioned more distally. Furthermore, although the primitive streak forms correctly, cells within the streak fail to undergo epithelial-to-mesenchymal transition, resulting in disrupted germ layer formation. Finally, the researchers show that, while Oct4 loss causes widespread changes in gene expression, no one particular signalling pathway appears to be affected, suggesting that Oct4 deletion instead results in the mis-regulation of key lineage specifiers. Overall, these findings highlight an essential role for Oct4 in orchestrating the correct patterning and specification of lineages in the postimplantation embryo.