ANTAGONISM OF CELL-ADHESION BY AN ALPHA-CATENIN MUTANT, AND OF THE WNT-SIGNALING PATHWAY BY ALPHA-CATENIN IN XENOPUS EMBRYOS

In Xenopus laevis development, beta-catenin plays an important role in the Wnt-signaling pathway by establishing the Nieuwkoop center, which in turn leads to specification of the dorsoventral axis. Cadherins ar e essential for embryonic morphogenesis since they mediate calcium-dep endent cell-cell adhesion and can modulate beta-catenin signaling. alp ha-catenin links beta-catenin to the actin-based cytoskeleton. To stud y the role of endogenous alpha-catenin in early development, we have m ade deletion mutants of alpha N-catenin. The binding domain of beta-ca tenin has been mapped to the NH2-terminal 210 amino acids of alpha N-c atenin. Overexpression of mutants lacking the COOH-terminal 230 amino acids causes severe developmental defects that reflect impaired calciu m-dependent blastomere adhesion. Lack of normal adhesive interactions results in a loss of the blastocoel in early embryos and ripping of th e ectodermal layer during gastrulation. The phenotypes of the dominant -negative mutants can be rescued by coexpressing full-length alpha N-c atenin or a mutant of beta-catenin that lacks the internal armadillo r epeats. We next show that coexpression of alpha N-catenin antagonizes the dorsalizing effects of beta-catenin and Xwnt-8. This can be seen p henotypically, or by studying the effects of expression on the downstr eam homeobox gene Siamois. Thus, alpha-catenin is essential for proper morphogenesis of the embryo and may act as a regulator of the intrace llular beta-catenin signaling pathway in vivo.