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© The Rockefeller University Press, 0021-9525/1997//1033 $5.00
The Journal of Cell Biology, Volume 139, Number 4, , 1997 1033-1046

Article

Antagonism of Cell Adhesion by an {alpha}-Catenin Mutant, and of the Wnt-signaling Pathway by {alpha}-Catenin in Xenopus Embryos



Ravinder N.M. Sehgal*, Barry M. Gumbiner{ddagger}, and Louis F. Reichardt*

* Cell Biology Program, Department of Biochemistry and Biophysics, and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724; and {ddagger} Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York 10021

In Xenopus laevis development, β-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 are essential for embryonic morphogenesis since they mediate calcium-dependent cell–cell adhesion and can modulate β-catenin signaling. {alpha}-catenin links β-catenin to the actin-based cytoskeleton. To study the role of endogenous {alpha}-catenin in early development, we have made deletion mutants of {alpha}N-catenin. The binding domain of β-catenin has been mapped to the NH2-terminal 210 amino acids of {alpha}N-catenin. Overexpression of mutants lacking the COOH-terminal 230 amino acids causes severe developmental defects that reflect impaired calcium-dependent blastomere adhesion. Lack of normal adhesive interactions results in a loss of the blastocoel in early embryos and ripping of the ectodermal layer during gastrulation. The phenotypes of the dominant-negative mutants can be rescued by coexpressing full-length {alpha}N-catenin or a mutant of β-catenin that lacks the internal armadillo repeats.

We next show that coexpression of {alpha}N-catenin antagonizes the dorsalizing effects of β-catenin and Xwnt-8. This can be seen phenotypically, or by studying the effects of expression on the downstream homeobox gene Siamois. Thus, {alpha}-catenin is essential for proper morphogenesis of the embryo and may act as a regulator of the intracellular β-catenin signaling pathway in vivo.

Abbreviations used in this paper: APC, adenomatous polyposis coli; DAI, dorsalizing index; GFP, green fluorescent protein.

The authors are deeply grateful to Dr. R. Kypta and Dr. F. Fagotto for helpful comments on the manuscript; Dr. Tabitha Doniach for help in analyzing Xenopus development; Dr. Isabel Fariñas for instruction in histology; Dr. Cindy Sholes, Dr. Uli Müller, and Mr. Kuanhong Wang for the development of important antibodies; and members of the Gumbiner laboratory for support.

Address all correspondence to Louis Reichardt, HHMI, Room U-426, UCSF, Box 0724, San Francisco, CA 94143-0724. Tel.: (415) 476-3976. Fax: (415) 476-9914. E-mail: lfr{at}cgl.ucsf.edu


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