► Snail and Sox3 are reciprocal direct transcriptional repressors ► Snail/Sox3 reciprocal repression defines ectodermal versus mesendodermal territories ► Snail2 induces cell delamination without inducing mesodermal or endodermal fates ► The Snail/Sox3 relationship is conserved in mouse embryos and human cancer cells. Here, SNAI1 is linked to cancer.