Article

An apical MRCK-driven morphogenetic pathway controls epithelial polarity

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Abstract

Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning-defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown. Here we show that the Cdc42 effector MRCK activates myosin-II at the apical pole to segregate aPKC–Par6 from junctional Par3, defining the apical domain. Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC–Par6 downregulating antagonistic RhoA-driven junctional actomyosin contractility, and drives polarization of cytosolic brush border determinants and apical morphogenesis. MRCK-activated polarized actomyosin contractility is required for apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors. Our results identify an apical origin of actomyosin-driven morphogenesis that couples cytoskeletal reorganization to PAR polarity signalling.

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Acknowledgements

This work was supported by the BBSRC (BB/L007584/1 and BB/N014855/1) and the Wellcome Trust (099173/Z/12/Z). Work in the F.P. laboratory, including support to E.V., was funded by an MRC grant (MC_UU_12018/3). The N2 A71 monoclonal antibodies, developed by E. Wieschaus, were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, Iowa 52242. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study.

Author information

Author notes

    • Evi Vlassaks
    •  & Stephen Terry

    Present addresses: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK (E.V.); Randall Division of Cell and Molecular Biophysics, King’s College London, SE1 1UL, UK (S.T.).

Affiliations

  1. Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK

    • Ceniz Zihni
    • , Stephen Terry
    • , Maria Susana Balda
    •  & Karl Matter
  2. MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK

    • Evi Vlassaks
    •  & Franck Pichaud
  3. Division of Cancer Studies, Section of Cell Biology and Imaging, King’s College London, London SE1 1UL, UK

    • Jeremy Carlton
  4. Institute of Molecular and Cell Biology, A-STAR, 61 Biopolis Drive, Singapore 138673, Singapore

    • Thomas King Chor Leung
  5. The Department of Anatomy, National University of Singapore, Singapore 119260, Singapore

    • Thomas King Chor Leung
  6. Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK

    • Michael Olson

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Contributions

C.Z. performed most of the vertebrate and E.V. the Drosophila experiments. All other authors performed particular subsets of experiments. C.Z., M.S.B. and K.M. designed the project and drafted the manuscript. All authors read and contributed to the final version of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Maria Susana Balda or Karl Matter.

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  1. 1.

    Induction of polarized myosin activation by Cdc42.

    Apical Cdc42 activation by conditional expression of Dbl3-myc in MDCK cells constitutively expressing EGFP-MLC was induced by adding tetracycline followed by recording image stacks every 5 min. Shown are projections of 4 images derived from the apical domain. The experiment was performed five times.