Primitive means first, not worst: Critical roles for primitive endoderm in embryos and embryo models.

In mammals, extraembryonic tissues, such as the placenta and yolk sac, are the first cell types to be specified during development because they enable the embryo to take residence and thrive in the uterine environment. Among extraembryonic tissue types, primitive endoderm (PrE), which will eventually contribute to the yolk sac, is especially fascinating. The PrE itself is named for functioning like the embryo's original gut-like tissue. For many years, our understanding of the PrE was limited by the intrinsically challenging nature of accessing and observing this tissue. However, pioneering studies in mouse have gradually revealed that the PrE is more than just nutritive in function. In fact, the PrE lineage gives rise to signaling centers that oversee developmental processes within the fetus - through processes that are very likely conserved between rodents and primates. Thus, understanding the stages between PrE and yolk sac promises clinically relevant models, including stem cell embryo models, which could lead to enhanced success for in vitro fertilization (IVF). Here, we examine the functions of PrE in the context of embryos, stem cells, and embryo models.