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 are essential for embryonic morphogenesis since they mediate calcium-dependent cell-cell adhesion and can modulate beta-catenin signaling. alpha-catenin links beta-catenin to the actin-based cytoskeleton. To study the role of endogenous alpha-catenin in early development, we have made deletion mutants of alphaN-catenin. The binding domain of beta-catenin has been mapped to the NH2-terminal 210 amino acids of alphaN-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 alphaN-catenin or a mutant of beta-catenin that lacks the internal armadillo repeats. We next show that coexpression of alphaN-catenin antagonizes the dorsalizing effects of beta-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 beta-catenin signaling pathway in vivo.
Sehgal
R N
RN
Cell Biology Program, Department of Biochemistry and Biophysics, and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724, USA.
Gumbiner
B M
BM
Reichardt
L F
LF
D000818:Animals; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000502:physiology*; D004627:Embryonic Induction; D005775:Gastrula / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics; D009024:Morphogenesis; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology*; D029961:Zebrafish Proteins; D051178:alpha Catenin; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; C093133:SIA1 protein, Xenopus; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051178:alpha Catenin; D051176:beta Catenin; C495248:wnt8a protein, Xenopus; D002118:Calcium