A primitive endoderm-centric view of mammalian development

ABSTRACT

The primitive endoderm (PE), or hypoblast in humans, is a conserved extra-embryonic lineage essential for mammalian development that fulfills key roles in embryo patterning, such as contributing to the gut endoderm, providing nutrient and gas exchange, and hosting the first wave of hematopoiesis. In this Review, we summarize our current understanding of PE development, focusing on the mouse and, where appropriate, the human context. We examine the molecular mechanisms involved in the segregation of the PE and epiblast lineages during pre-implantation development, exploring how stochastic processes and positional history initiate fate specification, and how robust ratio control of the two lineages is ensured. Furthermore, we evaluate the expanding repertoire of in vitro stem cell models of embryos, categorizing them according to their PE representation and functional utility in studying peri- and post-implantation development.