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Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila

Nature Cell Biology volume 15, pages 10451055 (2013) | Download Citation

Abstract

Planar cell polarity (PCP) is cellular polarity within the plane of an epithelial tissue or organ. PCP is established through interactions of the core Frizzled (Fz)/PCP factors and, although their molecular interactions are beginning to be understood, the upstream input providing the directional bias and polarity axis remains unknown. Among core PCP genes, Fz is unique as it regulates PCP both cell-autonomously and non-autonomously, with its extracellular domain acting as a ligand for Van Gogh (Vang). We demonstrate in Drosophila melanogaster wings that Wg (Wingless) and dWnt4 (Drosophila Wnt homologue) provide instructive regulatory input for PCP axis determination, establishing polarity axes along their graded distribution and perpendicular to their expression domain borders. Loss-of-function studies reveal that Wg and dWnt4 act redundantly in PCP determination. They affect PCP by modulating the intercellular interaction between Fz and Vang, which is thought to be a key step in setting up initial polarity, thus providing directionality to the PCP process.

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Acknowledgements

We are grateful to P. Adler, K. Choi, D. Strutt, G. Struhl, J-P. Vincent, S. Cohen, H. Bellen, the Bloomington Drosophila Stock Center and the DSHB for fly strains and reagents, and Benoit Aigouy for providing the ‘Packing Analyser V2.0’ software. We thank all Mlodzik laboratory members for helpful discussions and suggestions, G. Struhl and P. Lawrence for sharing unpublished results and discussion and Paul Wassarman, P. Olguin, W. Gault, G. Collu, L. Kelly and R. Krauss for helpful comments and suggestions on the manuscript. Confocal microscopy was carried out at the Microscopy Shared Resource Facility of the Icahn School of Medicine at Mount Sinai. This work was supported by a National Institutes of Health (NIGMS) grant to M.M.

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Affiliations

  1. Department of Developmental and Regenerative Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA

    • Jun Wu
    • , Jose Maria Carvajal-Gonzalez
    •  & Marek Mlodzik
  2. Instituto Cajal, CSIC, Av. Doctor Arce 37, 28002 Madrid, Spain

    • Angel-Carlos Roman

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Contributions

J.W. and M.M. planned the project, designed and carried out the experiments, analysed the data and wrote the paper; A.R. and J.C. analysed the data and designed quantitative analytical tools for the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Marek Mlodzik.

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https://doi.org/10.1038/ncb2806

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