Analysis of Dishevelled signalling pathways during Xenopus development

Analysis of Dishevelled signalling pathways during Xenopus development 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 block 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Biology Elsevier

Analysis of Dishevelled signalling pathways during Xenopus development

Current Biology, Volume 6 (11) – Nov 1, 1996

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Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Science Ltd
ISSN
0960-9822
DOI
10.1016/S0960-9822(96)00750-6
Publisher site
See Article on Publisher Site

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 block 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.

Journal

Current BiologyElsevier

Published: Nov 1, 1996

References

  • Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signalling cascade with noggin and follistatin
    McGrew, LL; Lai, C-J; Moon, RT
  • Functional conservation of the Wnt signalling pathway revealed by ectopic expression of Drosophila dishevelled in Xenopus
    Rothbacher, U; Laurent, MN; Blitz, IL; Watabe, T; Marsh, JL; Cho, KWY
  • Organizing the Xenopus organizer
    Gerhart, J; Doniach, T; Stewart, R
  • Overexpression of the homeobox gene Xnot-2 leads to notochord formation in Xenopus
    Gont, LK; Fainsod, A; Kim, S-H; De Robertis, EM
  • Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development
    Torres, MA; Yang-Snyder, JA; Purcell, SM; DeMarais, AA; McGrew, LL; Moon, RM

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