beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos

Mech Dev. 1998 Sep;77(1):75-80. doi: 10.1016/s0925-4773(98)00134-8.

Abstract

The Wnt/beta-catenin signaling pathway is responsible for the establishment of dorsoventral axis of Xenopus embryos. The recent finding of the F-box/WD40-repeat protein slimb in Drosophila, whose loss-of-function mutation causes ectopic activation of wingless signaling (Jiang, J., Struhl, G., 1998. Nature 391, 493-496), led us to examine the role of its vertebrate homolog betaTrCp in the Wnt/beta-catenin signaling and dorsal axis formation in Xenopus embryos. Co-injection of betaTrCp mRNA diminished Xwnt8 mRNA-induced axis formation and expression of Siamois and Xnr3, suggesting that betaTrCP is a negative regulator of the Wnt/beta-catenin signaling pathway. An mRNA for a betaTrCp mutant construct (DeltaF), which lacked the F-box domain, induced an ectopic axis and expression of Siamois and Xnr3. Because this activity of DeltaF was suppressed by co-injection of DeltaF TrCP mRNA, DeltaF likely acts in a dominant negative fashion. The activity of DeltaF was diminished by C-cadherin, glycogen synthase kinase 3 and Axin, but not by a dominant negative dishevelled. These results suggest that betaTrCp can act as a negative regulator of dorsal axis formation in Xenopus embryos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Body Patterning / physiology*
  • Cytoskeletal Proteins / physiology*
  • Embryo, Nonmammalian / physiology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Mutation
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Receptors, Transforming Growth Factor beta / genetics
  • Sequence Deletion
  • Signal Transduction
  • Trans-Activators*
  • Transforming Growth Factor beta*
  • Wnt Proteins
  • Xenopus / embryology*
  • Xenopus / physiology
  • Xenopus Proteins*
  • Zebrafish Proteins*
  • beta Catenin
  • beta-Transducin Repeat-Containing Proteins

Substances

  • BTRC protein, Xenopus
  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • Receptors, Transforming Growth Factor beta
  • SIA1 protein, Xenopus
  • Trans-Activators
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • beta-Transducin Repeat-Containing Proteins
  • nodal3.1 protein, Xenopus
  • GTP-Binding Proteins