Abstract
The first cell fate decisions during mammalian development establish tissues essential for healthy pregnancy. The mouse has served as a valuable model for discovering pathways regulating the first cell fate decisions because of the ease with which early embryos can be recovered and the availability of an arsenal of classical and emerging methods for manipulating gene expression. We summarize the major pathways that govern the first cell fate decisions in mouse development. This knowledge serves as a paradigm for exploring how emergent properties of a self-organizing system can dynamically regulate gene expression and cell fate plasticity. Moreover, it brings to light the processes that establish healthy pregnancy and ES cells. We also describe unsolved mysteries and new technologies that could help to overcome experimental challenges in the field.