Synthetic embryology: controlling geometry to model early mammalian development

Differentiation of embryonic stem cells in vitro is an important tool in dissecting and understanding the mechanisms that govern early embryologic development. In recent years, there has been considerable progress in creating organoids that model gastrulation, neurulation or organogenesis. However, one of the key challenges is reproducibility. Geometrically confining stem cell colonies considerably improves reproducibility and provides quantitative control over differentiation and tissue shape. Here, we review recent advances in controlling the two-dimensional or three-dimensional organization of cells and the effect on differentiation phenotypes. Improved methods of geometrical control will allow for an even more detailed understanding of the mechanisms underlying embryologic development and will eventually pave the way for the highly reproducible generation of specific tissue types.