TY - JOUR
T1 - Analysis of Dishevelled signalling pathways during Xenopus development
AU - Sokol, Sergei Y.
N1 - Funding Information:
I am grateful to E. Boncinelli for Xotx2 , E. De Robertis for chordin , R. Harland for Xnr3 , I. Dawid for Xlim1 , F. Watt for MZ15 antibodies, P. McCrea for β -catenin, D. Turner for pCS2 vectors, P. Wilson for Xbra and to A. Hemmati-Brivanlou for goosecoid plasmids. I thank K. Itoh, T. Holowacz, I. Drummond, J. Grinblat and N. Moghal for helpful comments on the manuscript, and M. Kapushchevsky for help with Figure 7 . This work was supported by NIH grant HD31247, the Jessie Cox Trust and the Massachusetts Medical Foundation.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030293782&partnerID=8YFLogxK
U2 - 10.1016/S0960-9822(96)00750-6
DO - 10.1016/S0960-9822(96)00750-6
M3 - Article
C2 - 8939601
AN - SCOPUS:0030293782
SN - 0960-9822
VL - 6
SP - 1456
EP - 1467
JO - Current Biology
JF - Current Biology
IS - 11
ER -