Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function

Curr Biol. 2021 Jun 2:S0960-9822(21)00680-1. doi: 10.1016/j.cub.2021.05.021. Online ahead of print.ABSTRACTThe 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 classic 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 (IFs) 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 in an in vitro competition assay and suprabasal tight junction barrier functions in 3D reconstructed epidermis. Surprisingly, disengaging desmosomes from IF also accelerated the expression of differentiation markers, through precocious activation of the mechanosensitive transcriptional regulator serum response factor (SRF) and downstream...
Source: Current Biology - Category: Biology Authors: Source Type: research
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