Suppression of ERK signalling abolishes primitive endoderm formation but does not promote pluripotency in rabbit embryo

Formation of epiblast (EPI) – the founder line of all embryonic lineages – and extra-embryonic supportive tissues is one of the key events in mammalian development. The prevailing model of early mammalian development is based almost exclusively on the mouse. Here we provide a comprehensive, stage-by-stage analysis of the EPI and extraembryonic primitive endoderm (PrE) formation during pre-implantation development of the rabbit. Whilst we observed that rabbit embryos have several features in common with mouse embryos, including a stage-related initiation of lineage specification, our results demonstrate the existence of some key differences in lineage specification among mammals. Contrary to the current view, our data suggest that reciprocal repression of GATA6 and NANOG is not fundamental for initial stages of PrE versus EPI specification in mammals. Furthermore, our results provide insight into the observed discrepancies between the role of FGF/ERK signalling in PrE versus EPI specification, between mouse and other mammals.