Stem Cell Models of Mammalian Gastrulation

Understanding how embryos build a body plan has long relied on two complementary yet somewhat contrasting ideas: that organizers act as sources of positional information, and that self-organizing systems generate spatial order through local unsupervised interactions. This essay explores these concepts from the perspective of pluripotent stem cells (PSCs) and the process of gastrulation. Here, I first briefly discuss the properties of PSCs, and then outline how, under controlled cultured conditions, these self-organize into structures-replicas and models of early embryos-that display the main features of mammalian gastrulation: the establishment of polarity, a coordinate system, and axial organization. These features act as references for the unfolding of spatiotemporally coordinated gene expression programs that characterize the mammalian body plan. These systems have been key to gathering important insights about the mechanisms that lay down the mammalian body plan. One of these PSC-based structures, "gastruloids," reveal properties of developmental systems that cannot be accessed in embryos, namely, a surprising separation of morphogenesis and gene expression maps. As such, gastruloids offer a practical platform to experimentally reconcile the concepts of self-organization and embryonic organizers.