From embryos to embryoids: How external signals and self-organization drive embryonic development

Embryonic development has been traditionally seen as an inductive process directed by exogenous maternal inputs and extra-embryonic signals. Increasing evidence, however, is showing that, in addition to exogenous signals, the development of the embryo involves endogenous self-organization. Recently, this self-organizing potential has been highlighted by a number of stem cell models known as embryoids that can recapitulate different aspects of embryogenesis in vitro. Here, we review the self-organizing behaviors observed in different embryoid models and seek to reconcile this new evidence with classical knowledge of developmental biology. This analysis leads to reexamine embryonic development as a guided self-organizing process, where patterning and morphogenesis are controlled by a combination of exogenous signals and endogenous self-organization. Finally, we discuss the multidisciplinary approach required to investigate the genetic and cellular basis of self-organization.