Desmoplakin is essential in epidermal sheet formation

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