Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding

Abstract

Epithelial planar cell polarity (PCP) is evident in the cellular organization of many tissues in vertebrates and invertebrates1,2,3,4,5. In mammals, PCP signalling governs convergent extension during gastrulation and the organization of a wide variety of structures, including the orientation of body hair and sensory hair cells of the inner ear6,7. In Drosophila melanogaster, PCP is manifest in adult tissues, including ommatidial arrangement in the compound eye and hair orientation in wing cells1,2,4. PCP establishment requires the conserved Frizzled/Dishevelled PCP pathway1,2,3,4,5. Mutations in PCP-pathway-associated genes cause aberrant orientation of body hair or inner-ear sensory cells in mice6,7, or misorientation of ommatidia and wing hair in D. melanogaster1,2,4. Here we provide mechanistic insight into Frizzled/Dishevelled signalling regulation. We show that the ankyrin-repeat protein Diego binds directly to Dishevelled and promotes Frizzled signalling. Dishevelled can also be bound by the Frizzled PCP antagonist Prickle8. Strikingly, Diego and Prickle compete with one another for Dishevelled binding, thereby modulating Frizzled/Dishevelled activity and ensuring tight control over Frizzled PCP signalling.

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Figure 1: dgo is required in the R3 photoreceptor.
Figure 2: Genetic interactions of dgo with other PCP factors.
Figure 3: Dgo competes with Pk for Dsh binding.
Figure 4: Dgo and Pk compete with each other in vivo.
Figure 5: Model of how Dgo and the Pk–Stbm complex differentially affect Dsh and Fz PCP signalling in R3 and R4.

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Acknowledgements

We thank D. Gubb, K. Basler, T. Wolff and the Bloomington stock center for fly strains, P. James for yeast strains, and J. Suriano and Z.-F. Du for technical help. We thank E. Wurmbach, R. Krauss and members of the Mlodzik laboratory for critically reading the manuscript. The work has been supported by NIH grant RO1 GM62917 to M.M. A.J. was supported in part by Swiss National Science Foundation grant 823A-64689.

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Correspondence to Marek Mlodzik.

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Supplementary figures S1 and S2; supplementary table S1 (PDF 349 kb)

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Jenny, A., Reynolds-Kenneally, J., Das, G. et al. Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding. Nat Cell Biol 7, 691–697 (2005). https://doi.org/10.1038/ncb1271

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