EMBRYONIC AXIS INDUCTION BY THE ARMADILLO REPEAT DOMAIN OF BETA-CATENIN - EVIDENCE FOR INTRACELLULAR SIGNALING

beta-catenin was identified as a cytoplasmic cadherin-associated prote in required for cadherin adhesive function (Nagafuchi, A., and M. Take ichi. 1989. Cell Regul. 1:37-44; Ozawa, M., H. Baribault, and R. Kemle r. 1989. EMBO [Eur. Mel. Biol. Organ.] J. 8:1711-1717). Subsequently, it was found to be the vertebrate homologue of the Drosophila segment polarity gene product Armadillo (McCrea, P. D., C. W. Turck, and B. Gu mbiner. 1991. Science [Wash. DC]. 254:1359-1361; Peifer, M., and E. Wi eschaus. 1990. Cell. 63:1167-1178). Also, antibody perturbation experi ments implicated beta-catenin in axial patterning of the early Xenopus embryo (McCrea, P. D., W. M. Brieher, and B. M. Gumbiner. 1993. J. Ce ll Biol. 123:477-484). Here we report that overexpression of beta-cate nin in the ventral side of the early Xenopus embryo, by injection of s ynthetic beta-catenin mRNA, induces the formation of a complete second ary body axis. Furthermore, an analysis of beta-catenin deletion const ructs demonstrates that the internal armadillo repeat region is both n ecessary and sufficient to induce axis duplication. This region intera cts with C-cadherin and with the APC tumor suppressor protein, but not with alpha-catenin, that requires the amino-terminal region of beta-c atenin to bind to the complex. Since alpha-catenin is required for cad herin-mediated adhesion, the armadillo repeat region alone probably ca nnot promote cell adhesion, making it unlikely that beta-catenin induc es axis duplication by increasing cell adhesion. We propose, rather, t hat beta-catenin acts in this circumstance as an intracellular signali ng molecule. Subcellular fractionation demonstrated that all of the be ta-catenin constructs that contain the armadillo repeat domain were pr esent in both the soluble cytosolic and the membrane fraction. Immunof luorescence staining confirmed the plasma membrane and cytoplasmic loc alization of the constructs containing the armadillo repeat region, bu t revealed that they also accumulate in the nucleus, especially the co nstruct containing only the armadillo repeat domain. These findings an d the beta-catenin protein interaction data offer several intriguing p ossibilities for the site of action or the protein targets of beta-cat enin signaling activity.