Desmosomes pattern cell mechanics to govern epidermal tissue form and function

Joshua A. Broussard, Jennifer L. Koetsier, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermis is a stratified epithelium in which structural and functional features are polarized across multiple cell layers. This type of polarity is essential for establishing the epidermal barrier, but how it is created and sustained is poorly understood. Previous work identified a role for the classical cadherin/filamentous-actin network in establishment of epidermal polarity. However, little is known about potential roles of the most prominent epidermal intercellular junction, the desmosome, in establishing epidermal polarity, in spite of the fact that desmosome constituents are patterned across the apical to basal cell layers. Here, we show that desmosomes and their associated intermediate filaments (IF) are key regulators of mechanical polarization in epidermis, whereby basal and suprabasal cells experience different forces that drive layer-specific functions. Uncoupling desmosomes and IF or specific targeting of apical desmosomes through depletion of the superficial desmosomal cadherin, desmoglein 1, impedes basal (stratification) and suprabasal (tight junction barrier) functions. Surprisingly, disengaging desmosomes from IF also uncouples stratification from differentiation, accelerating the expression of differentiation markers. Our data support a model in which the desmosome-IF network supports a reciprocally organized distribution of ErbB1/EGFR activity in the basal layer and mechanosensitive kinase ErbB2 activity in the suprabasal layer to ensure the proper spatiotemporal coordination of cell mechanics and the biochemical program of differentiation.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jan 21 2020

Keywords

  • cell and tissue mechanics
  • Desmosomes
  • epidermal morphogenesis
  • epithelial polarity
  • ErbB proteins
  • intermediate filaments
  • the cytoskeleton
  • tight junctions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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