Analysis of Dishevelled signalling pathways during Xenopus development

Research output: Contribution to journalArticlepeer-review

363 Scopus citations

Abstract

Background: Recent studies have demonstrated that the Wnt, Frizzled and Notch proteins are involved in a variety of developmental processes in fly, worm, frog and mouse embryos The Dishevelled (Dsh) protein is required for Drosophila cells to respond to Wingless, Notch and Frizzled signals, but the molecular mechanisms of its action are not well understood. Using the ability of a mutant form of the Xenopus homologue of Dsh (Xdsh) to black Wnt and Dsh signalling in a model system, this work attempts to clarify the role of the endogenous Xdsh during the early stages of vertebrate development. Results: A mutant Xdsh (Xdd1) with an internal deletion of the conserved PDZ/DHR domain was constructed. Overexpression of Xdd1 mRNA in ventral blastomeres of Xenopus embryos strongly inhibited induction of secondary axes by the wild- type Xdsh and Xwnt8 mRNAs, but did not affect the axis-inducing ability of β-catenin mRNA. These observations suggest that Xdd1 acts as a dominant negative mutant. Dorsal expression of Xdd1 caused severe posterior truncations in the injected embryos, whereas wild-type Xdsh suppressed this phenotype. Xdd1 blocked convergent extension movements in ectodermal explants stimulated with mesoderm-inducing factors and in dorsal marginal zone explants, but did not affect mesoderm induction and differentiation. Conclusions: A vertebrate homologue of Dsh is a necessary component of Wnt signal transduction and functions upstream of β-catenin. These findings also establish a requirement for the PDZ domain in signal transduction by Xdsh, and suggest that endogenous Xdsh controls morphogenetic movements in the embryo.

Original languageEnglish
Pages (from-to)1456-1467
Number of pages12
JournalCurrent Biology
Volume6
Issue number11
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Dive into the research topics of 'Analysis of Dishevelled signalling pathways during Xenopus development'. Together they form a unique fingerprint.

Cite this