Early mammalian embryos exhibit remarkable plasticity, as highlighted by the ability of separated early blastomeres to produce a whole organism. Recent work in the mouse implicates a network of transcription factors in governing the establishment of the primary embryonic lineages. A combination of genetics and embryology has uncovered the organisation and function of the components of this network, revealing a gradual resolution from ubiquitous to lineage-specific expression through a combination of defined regulatory relationships, spatially organised signalling, and biases from mechanical inputs. Here, we summarise this information, link it to classical embryology and propose a molecular framework for the establishment and regulation of developmental plasticity.