The field of developmental biology has been revolutionized by the advent of stem cell-based modeling of embryonic development, which enables the generation of nearly every cell type in the body from embryonic or induced pluripotent stem cells (PSCs). Through combinations of three-dimensional (3D) aggregation, embedding, micropatterned culture, microfluidics, targeted injections, and more, researchers can mimic the cell fate trajectories of pre-, peri-, and post- gastrulation embryos in vitro. Beyond providing raw material for directed differentiation, these in vitro models may enable rare glimpses into embryonic processes that are otherwise difficult or impossible to study, such as mammalian peri-implantation development. Furthermore, technical and ethical limitations largely prevent the experimentation and observation necessary to determine whether developmental mechanisms described in research organisms are conserved in human embryos. By generating and further refining embryo-like structures from human stem cells, researchers hope to gain previously inaccessible knowledge about human embryogenesis.

Despite major advances in in vitro modeling of development, most stem cell-based models do not yet faithfully recapitulate one critical aspect of embryogenesis: morphogenesis. Morphogenetic movements position cells within signaling gradients and shape collections of cells into functional tissues and organs. Without these cell- and tissue-level behaviors, any model of development – no matter how well it represents an array of cell types – is incomplete. It is indeed possible to induce morphogenetic programs within cells that otherwise would not exhibit such behaviors, and this building of embryonic form “from scratch” is the primary goal of the growing field of synthetic morphogenesis. Here, we review several examples of synthetic morphogenesis - with a focus on those resembling gastrulation and the surrounding stages - to examine the morphogenetic programs that are best approximated by culture models and consider opportunities for improvement on current approaches.