Primitive streak formation and mesoderm development during gastrulation require canonical Wnt signalling. However, determining how it regulates these complex early developmental stages in vivo is a considerable challenge. So Lindsley and colleagues turned to mouse embryonic stem (ES) cells, where they studied the role of canonical Wnt signalling in their differentiation and discovered that it is required for mesoderm induction (see p. 3787). ES cells in which canonical Wnt signalling is inhibited by Dikkopf1, these authors report,fail to generate mesodermal precursor cells. Without Wnt signalling, the differentiating ES cells fail to express genes that are associated in vivo with the development of the primitive streak or with the nascent mesoderm and endoderm lineages. They also report that Wnt signalling alone is insufficient to induce mesodermal gene expression but that it is required during this process and acts cooperatively with Bmp signalling. Overall, these results suggest that Wnt signalling regulates the responsiveness of early embryos to other effector pathways during germ layer induction.