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Desmosomal adhesion regulates epithelial morphogenesis and cell positioning

Nature Cell Biology volume 3, pages 823–830 (2001)Cite this article

Abstract

Desmosomes are intercellular junctions of epithelia and are of widespread importance in the maintenance of tissue architecture. We provide evidence that desmosomal adhesion has a function in epithelial morphogenesis and cell-type-specific positioning. Blocking peptides corresponding to the cell adhesion recognition (CAR) sites of desmosomal cadherins block alveolar morphogenesis by epithelial cells from mammary lumen. Desmosomal CAR-site peptides also disrupt positional sorting of luminal and myoepithelial cells in aggregates formed by the reassociation of isolated cells. We demonstrate that desmosomal cadherins and E-cadherin are comparably involved in epithelial morphoregulation. The results indicate a wider role for desmosomal adhesion in morphogenesis than has previously been considered.

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Figure 1: Analysis of desmosomal cadherin expression in mammary luminal and myoepithelial cells.
Figure 2: Immunolocalization of cadherins in human and bovine non-pregnant mammary gland.
Figure 3: Desmocollin and desmoglein isoforms in mouse mammary gland primary cell cultures and cell lines.
Figure 4: Anti-adhesion peptides perturb alveolus-like morphogenesis of luminal mammary epithelial cells.
Figure 5: Luminal and myoepithelial cells sort out in rotary culture to form aggregates consisting of a cellular organization resembling that found in vivo.
Figure 6: Localization of integrins, but not BM components, to the outer surface of sorted aggregates.
Figure 7: Anti-adhesion peptides perturb myoepithelial cell sorting to the outside of aggregates.

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Acknowledgements

We thank Sue Davies for performing the cell sorting and culture of the human breast epithelia, Sarah Kirk for technical assistance with the electron microscopy, and Steve Bagley for advice on the confocal microscopy. This work was supported by the Medical Research Council and the Wellcome Foundation.

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Authors and Affiliations

  1. School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Oxford Road, Manchester, M13 9PT, UK

    Sarah K. Runswick, Charles H. Streuli & David R. Garrod

  2. LICR/UCL Breast Cancer Laboratory, 67–73 Riding House Street, London, W1W 4EJ, UK

    Mike J. O'Hare

  3. Department of Pathology, University of Leicester, Leicester Royal Infirmary, Leicester, LE2 7LX, UK

    Louise Jones

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Correspondence to David R. Garrod.

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Runswick, S., O'Hare, M., Jones, L. et al. Desmosomal adhesion regulates epithelial morphogenesis and cell positioning. Nat Cell Biol 3, 823–830 (2001). https://doi.org/10.1038/ncb0901-823

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