BETA-TRCP IS A NEGATIVE REGULATOR OF THE WNT BETA-CATENIN SIGNALING PATHWAY AND DORSAL AXIS FORMATION IN XENOPUS EMBRYOS/

The Wnt/beta-catenin signaling pathway is responsible for the establis hment of the dorsoventral axis of Xenopus embryos. The recent finding of the F-box/WD40-repeat protein slimb in Drosophila, whose loss-of-fu nction mutation causes ectopic activation of wingless signaling (Jiang , J., Struhl, G., 1998. Nature 391, 493-496), led us to examine the ro le of its vertebrate homolog beta-TrCP in Wnt/beta-catenin signaling a nd dorsal axis formation in Xenopus embryos. Co-injection of beta-TrCP mRNA diminished Xwnt8 mRNA-induced axis formation and expression of S iamois and Xnr3, suggesting that beta-TrCP is a negative regulator of the Wnt/beta-catenin signaling pathway. An mRNA for a beta-TrCP mutant construct (Delta F), which lacked the F-box domain, induced an ectopi c axis and expression of Siamois and Xnr3. Because this activity of De lta F was suppressed by co-injection of beta-TrCP mRNA, Delta F likely acts in a dominant negative fashion. The activity of Delta F was dimi nished by C-cadherin, glycogen synthase kinase 3 and Axin, but not by a dominant negative dishevelled. These results suggest that beta-TrCP can act as a negative regulator of dorsal axis formation in Xenopus em bryos. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.