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

Abstract

The Wnt/β-catenin signaling pathway is responsible for the establishment of the 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 β-TrCP in Wnt/β-catenin signaling and dorsal axis formation in Xenopus embryos. Co-injection of β-TrCP mRNA diminished Xwnt8 mRNA-induced axis formation and expression of Siamois and Xnr3, suggesting that β-TrCP is a negative regulator of the Wnt/β-catenin signaling pathway. An mRNA for a β-TrCP mutant construct ( ΔF), which lacked the F-box domain, induced an ectopic axis and expression of Siamois and Xnr3. Because this activity of ΔF was suppressed by co-injection of β-TrCP mRNA, ΔF likely acts in a dominant negative fashion. The activity of ΔF was diminished by C-cadherin, glycogen synthase kinase 3 and Axin, but not by a dominant negative dishevelled. These results suggest that β-TrCP can act as a negative regulator of dorsal axis formation in Xenopus embryos.