Our studies demonstrate that Tbx2 functions as a transcriptional repressor during germ layer formation, and suggest that this activity is mediated in part through repression of target genes that are stimulated, in the mesendoderm, by transactivating T-box proteins. Taken together, our results point to a critical role for Tbx2 in limiting the potency of blastula-stage progenitor cells during vertebrate germ layer differentiation. Developmental Dynamics 247:903-913, 2018. © 2018 Wiley Periodicals, Inc.