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Desmoplakin is essential in epidermal sheet formation

Nature Cell Biology volume 3, pages 1076–1085 (2001)Cite this article

Abstract

We have generated an epidermis-specific desmoplakin (DP) mouse knockout, and show that epidermal integrity requires DP; mechanical stresses to DP-null skin cause intercellular separations. The number of epidermal desmosomes in DP-null skin is similar to wild type (WT), but they lack keratin filaments, which compromise their function. DP-null keratinocytes have few desmosomes in vitro, and are unable to undergo actin reorganization and membrane sealing during epithelial sheet formation. Adherens junctions are also reduced. In vitro, DP transgene expression rescues these defects. DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion.

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Figure 1: Generation of a conditional DP knockout in mouse skin epidermis.
Figure 2: Abnormalities in DP-null skin and in cornified envelope formation.
Figure 3: Ultrastructural analysis of intercellular adhesion in WT and DP-null skin.
Figure 4: Localization of adhesion, cytoskeleton and basement membrane proteins in DP-null epidermis.
Figure 5: Relative levels of expression of cell–cell adhesion proteins in DP-null versus wild-type epidermal cells in vivo and in vitro.
Figure 6: Aberrations in DP-null cell–cell junctions and KF-cell border attachments in vitro, and their rescue by gene transfection.
Figure 8: Ultrastructural analysis of cell–cell junctions in DP-null keratinocytes.
Figure 7: Aberrations in actin reorganization and epithelial sheet formation in DP-null keratinocytes.

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Acknowledgements

We thank I. King, J. Stanley; W. Franke for gifts of antibodies:. We especially thank A. Kobielak for carrying out the northern analysis. E.F. is an Investigator of the Howard Hughes Medical Institute. This work was supported by a grant to E.F. awarded by the National Institutes of Health (R01-AR27883).

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  1. Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, 60637, Illinois, USA

    Valeri Vasioukhin, Ethan Bowers, Christoph Bauer, Linda Degenstein & Elaine Fuchs

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Vasioukhin, V., Bowers, E., Bauer, C. et al. Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol 3, 1076–1085 (2001). https://doi.org/10.1038/ncb1201-1076

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