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Frodo interacts with Dishevelled to transduce Wnt signals

Nature Cell Biology volume 4, pages 351–357 (2002)Cite this article

Abstract

Dishevelled (Dsh) is required for the specification of cell fate and polarity by secreted Wnt proteins. Frodo, a novel conserved Dsh-binding protein, synergized with Xenopus Dsh (XDsh) in secondary axis induction in Xenopus laevis embryos. A dominant inhibitory construct and antisense oligonucleotide-mediated depletion of Frodo inhibited axial development in response to XDsh and XWnt8, and suppressed transcriptional activation of a reporter construct. At later embryonic stages, both dominant negative Frodo and antisense oligonucleotides interfered with the expression of regional neural markers and caused eye deficiencies, indicating that Frodo is required for normal eye and neural tissue development. Full-length Frodo RNA suppressed these loss-of-function phenotypes, attesting to their specificity. These findings establish a function for Frodo as an essential positive regulator of Wnt signalling.

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Figure 1: Deduced amino acid sequence and conserved regions of Frodo.
Figure 2: Expression of Frodo RNA during embryonic development.
Figure 3: Identification of protein domains involved in the Frodo–XDsh interaction.
Figure 4: The effects of Frodo and FrdC on Dsh activity.
Figure 5: Frodo functions upstream of the β-catenin degradation complex in axis induction.
Figure 6: Suppression of Dsh function in Frodo-depleted embryos.
Figure 7: An essential function of Frodo in eye development.
Figure 8: Eye and neural tissue abnormalities in Frodo-depleted embryos.

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Acknowledgements

We thank K. Itoh for the initial identification of Frodo fragments in the yeast two-hybrid screen. We are grateful to I. Dawid, J. Graff, B. Gumbiner, A. Hemmati-Brivanlou, R. Harland, M. Jamrich, P. Lemaire, R. Moon, E. De Robertis and J. Smith for plasmids, and T. Komiya for the Xenopus ovary cDNA λZAP library. We also thank J. Green, Y. Kamberov and M. Ratcliffe for comments on the manuscript. This work was supported by the grants from the March of Dimes Birth Defects Foundation and the National Institutes of Health to S.S. and the Deutsche Forschungsgemeinschaft to J.G.

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  1. Department of Microbiology and Molecular Genetics, Harvard Medical School, and Molecular Medicine Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, 02215, MA, USA

    Joachim Gloy, Hiroki Hikasa & Sergei Y. Sokol

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Gloy, J., Hikasa, H. & Sokol, S. Frodo interacts with Dishevelled to transduce Wnt signals. Nat Cell Biol 4, 351–357 (2002). https://doi.org/10.1038/ncb784

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