One of the first patterning events of embryogenesis occurs during gastrulation: three-dimensional (3D) cell movements reorganise the embryo, a mass of morphologically similar cells, into an axially organised structure with three germinal layers (endoderm, mesoderm and ectoderm). To date, two-dimensional (2D) culture models have failed to recapitulate such complex cell behaviours linking cell movement to cell fate. Here (p. ), Alfonso Martinez Arias and colleagues show that 3D aggregates of mouse embryonic stem cells cultured in mesendoderm-promoting medium undergo cell movements, axial organisation and germ layer specification, features reminiscent of gastrulation. They demonstrate that the expression of endoderm (Sox17, Fox2A) and early mesoderm (Brachyury) markers becomes polarised in these aggregates. Later, cells originating from the Brachyury-expressing ‘territory’ are extruded from the aggregate. These ‘gastruloids’ thus present a powerful tool that can be used to study early embryonic tissue specification in a dish, an unprecedented feat in vitro.
