Evidence that dorsal-ventral differences in gap junctional communication in the early Xenopus embryo are generated by beta-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 beta-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 beta-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 beta-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 beta-catenin mRNA can restore elevated levels of dorsal GJC when injected into beta-catenin-deficient oocytes, demonstrating the specificity of the beta-catenin depletion with the antisense oligonucleotides. Thus, endogenous beta-catenin is required for the observed differential GJC. This regulation of GJC is the earliest known action of the dorsal regulator, beta-catenin, in Xenopus development. Two lines of evidence, presented here, indicate that beta-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 beta-catenin (i.e., the ARM region), that lacks the cadherin-binding domain, restores dorsal GJC to beta-catenin-depleted embryos. Thus, beta-catenin appears to regulate GJC independent of its role in cell-cell adhesion, by acting within the cytoplasm through a signaling mechanism.
Krufka
A
A
Department of Genetics and Cell Biology, University of Minnesota, St. Paul, Minnesota, 55108, USA.
Johnson
R G
RG
Wylie
C C
CC
Heasman
J
J
D000818:Animals; D051186:Armadillo Domain Proteins; D001757:Blastomeres; D019521:Body Patterning; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion; D002450:Cell Communication; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D029721:Drosophila Proteins; D017629:Gap Junctions / Q000502:physiology*; D019476:Insect Proteins / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015534:Trans-Activators; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins; D051176:beta Catenin
D051186:Armadillo Domain Proteins; C495266:CTNNB1 protein, Xenopus; D015820:Cadherins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D016376:Oligonucleotides, Antisense; D015534:Trans-Activators; D029867:Xenopus Proteins; D051176:beta Catenin