CK2 is expressed widely in early embryonic development in several animal models, however its developmental role is unclear. One of the substrates of CK2 that is important in embryonic development is beta-catenin, the transcriptional co-activator of the canonical Wnt signaling pathway. This pathway has been implicated in diverse aspects of embryonic development, including one of the earliest events in embryonic development, the establishment of the dorso-ventral embryonic axis. In Xenopus laevis, dorso-ventral axis formation is dependent upon stabilization of beta-catenin in the future dorsal side of the embryo. Since CK2 phosphorylation of beta-catenin stabilizes it, we hypothesized that CK2 might be critical to upregulation of beta-catenin in Xenopus embryos and to the process of axis establishment. Our results demonstrate that CK2 is required for dorsal axis formation and is for normal upregulation of Wnt signaling genes and targets. Thus, CK2 is a regulator of endogenous axis formation in vertebrates.