During early embryonic development, the overall body plan and major axes are established through the process of gastrulation. Gastrulation proceeds with dynamic, organized cell migration that requires changes in cell adhesion and an epithelial to mesenchymal transition (EMT). The initiating step in gastrulation involves extensive cell mixing as mesenchymal cells migrate to the presumptive midline and form the primitive streak. The primitive streak is the site at which epiblast cells undergo EMT and ingress to form distinct cell layers that will become the primary germ layers, mesoderm and endoderm. Epiblast cells that do not ingress differentiate to become ectoderm. Intercellular signaling mediated by factors such as Wnt, FGF, and Nodal/TGF-beta ligands activate transcriptional programs that influence cell migration during gastrulation and subsequent cell differentiation into the three germ layers.