Article | Published:

Wdr1-mediated cell shape dynamics and cortical tension are essential for epidermal planar cell polarity

Nature Cell Biology volume 17, pages 592604 (2015) | Download Citation

Abstract

During mouse development, core planar cell polarity (PCP) proteins become polarized in the epidermal plane to guide angling/morphogenesis of hair follicles. How PCP is established is poorly understood. Here, we identify a key role for Wdr1 (also known as Aip1), an F-actin-binding protein that enhances cofilin/destrin-mediated F-actin disassembly. We show that cofilin and destrin function redundantly in developing epidermis, but their combined depletion perturbs cell adhesion, cytokinesis, apicobasal polarity and PCP. Although Wdr1 depletion accentuates single-loss-of-cofilin/destrin phenotypes, alone it resembles core PCP mutations. Seeking a mechanism, we find that Wdr1 and cofilin/destrin-mediated actomyosin remodelling are essential for generating or maintaining cortical tension within the developing epidermal sheet and driving the cell shape and planar orientation changes that accompany establishment of PCP in mammalian epidermis. Our findings suggest intriguing evolutionary parallels but mechanistic modifications to the distal wing hinge-mediated mechanical forces that drive cell shape change and orient PCP in the Drosophila wing disc.

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Acknowledgements

We thank D. Devenport, S. Williams, S. Beronja, A. R. Folgueras, D. Schramek, I. Matos and E. Ezratty for intellectual input; D. Oristian and A. Aldeguer as mouse specialists; Comparative Bioscience Center (AAALAC accredited) for care of mice in accordance with National Institutes of Health (NIH) guidelines; Bioimaging Center (A. North, director) for advice; Flow Cytometry facility (S. Mazel, director) for FACS sorting. Cfl–GFP was a generous gift from J. Condeelis (Albert Einstein college of Medicine, New York, USA); E.F. is an Investigator of the Howard Hughes Medical Institute. This research was supported by a grant from the NIH (R37-AR27883, E.F.), a Starr Stem Cell Postdoctoral Fellowship (C.L.) and a Genetics Training Grant by the NIH (E.H.).

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Author notes

    • Chen Luxenburg

    Present address: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

    • Chen Luxenburg
    •  & Evan Heller

    These authors contributed equally to this work.

Affiliations

  1. The Rockefeller University, Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, New York, New York 10065, USA

    • Chen Luxenburg
    • , Evan Heller
    • , H. Amalia Pasolli
    • , Sophia Chai
    • , Maria Nikolova
    • , Nicole Stokes
    •  & Elaine Fuchs

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Contributions

C.L. and E.F. conceived the study. C.L., E.H. and E.F. designed the experiments. C.L. and E.H. carried out the experiments and analysed the data. H.A.P. performed the ultrastructural analyses (Supplementary Fig. 1S). S.C. made the Wdr1-rescue construct, C.L. and N.S. performed the in utero injections. C.L. and M.N. prepared high-titre viruses. C.L., E.H. and E.F. wrote the paper. All authors provided intellectual input, vetted and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Elaine Fuchs.

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https://doi.org/10.1038/ncb3146

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