Evidence that dorsal-ventral differences in gap junctional communication in the early Xenopus embryo are generated by β-catenin independent of cell adhesion effects

Gap junctional communication (GJC) is regulated in the early Xenopus embryo and quantitative differences in junctional communication correlate with the specification of the dorsal-ventral axis. To address the mechanism that is responsible for regulating this differential communication, we investigated the function of β-catenin during the formation of the dorsal- ventral axis in Xenopus embryos by blocking its synthesis with antisense oligodeoxynucleotides. This method has previously been shown to reduce the level of β-catenin in the early embryo, prior to zygotic transcription, and to inhibit the formation of the dorsal axis (Heasman et al., 1994, Cell 79, 791-803). We show here that antisense inhibition of β-catenin synthesis also reduces GJC among cells in the dorsal hemisphere of 32-cell embryos to levels similar to those observed among ventral cells. Full-length β-catenin mRNA can restore elevated levels of dorsal GJC when injected into β-catenin- deficient oocytes, demonstrating the specificity of the β-catenin depletion with the antisense oligonueleotides. Thus, endogenous β-catenin is required for the observed differential GJC. This regulation of GJC is the earliest known action of the dorsal regulator, β-catenin, in Xenopus development. Two lines of evidence, presented here, indicate that β-catenin acts within the cytoplasm to regulate GJC, rather than through an effect on cell adhesion. First, when EP-cadherin is overexpressed and increased adhesion is observed, embryos display both a ventralized phenotype and reduced dye transfer. Second, a truncated form of β-catenin (i.e., the ARM region), that lacks the cadherin-binding domain, restores dorsal GJC to β-catenin-depleted embryos. Thus, β-catenin appears to regulate GJC independent of its role in cell- cell adhesion, by acting within the cytoplasm through a signaling mechanism.