CXXC Finger Protein 4 (CXXC4)

Cxxc4 interaction with the DVL1 PDZ domain competed with DVL1-Axin binding, and the affinity of DVL1 for Axin was higher than that of DVL1 for Cxxc4. In mouse fibroblasts, Cxxc4 suppressed Wnt3a induction of beta-catenin (CTNNB1) and inhibited Wnt3a-dependent Tcf4 (TCF7L2) activation, suggesting that Cxcc4 acts as a negative regulator of the Wnt signaling pathway and functions between DVL and beta-catenin. Dorsal injection of Cxxc4 mRNA into Xenopus embryos caused ventralization phenotypes such as loss of the head structure, while ventrally injected embryos developed normally. The findings suggested that Cxxc4 had ventralizing activity and that the C-terminal region may be sufficient to regulate embryonic axis formation.