Originally, a homologue of the vertebrate β-catenin was identified as a segment polarity gene involved in the wingless pathway in Drosophila melanogaster. Because of the structural organization of the gene, it was named armadillo (ARM), showing several repeats of a 42-amino acid motif in its central region (ARM-repeats) flanked by N-terminal and C-terminal regulatory domains. Its vertebrate homologues, β-catenin and γ -catenin (also named plakoglobin), were first characterized as structural proteins involved in cell adhesion, linking the cytoplasmic tail of type 1 cadherins (E, N-, P-, VE-cadherin) via α-catenin to the actin cytoskeleton. Although β-catenin is specific for classical cadherins of the adherens junction (AJ) complex, γ -catenin also associates with the desmosomal cadherins, desmocollin, and desmoglein, linking them via desmoplakin to the vimentin intermediate filament system. Due to its high sequence similarity to armadillo, a signaling function was also suggested for β-catenin and γ -catenin and was subsequently demonstrated by loss- and gain-of-function experiments in Xenopus laevis, leading to ventralized embryos and axis duplication, respectively (1). Furthermore, similar to the wingless growth factor in Drosophila, vertebrate Wnts, on binding to frizzled (Fz) receptors, stabilize cytoplasmic β-catenin or γ -catenin, leading to their activation in nuclear signaling. To accomplish this function, β-catenin interacts with HMG-box transcription factors of the lymphoid enhancer binding factor/ T-cell factor (Lef/TCF) family, which mediate DNA binding and thus enable the transactivating function of β-catenin.

The Wnt signaling pathway was initially characterized in development, where it was shown to be involved in processes as diverse as somitogenesis, and brain, limb, and vascular differentiation.