Plakoglobin as a Regulator of Desmocollin Gene Expression

Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages and the heart. The goal of the present study was to investigate how desmocollins (DSC), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with Lef-1 differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NFκB pathway components, down-stream effectors of the Eda/EDAR signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and Eda/EDAR/NFκB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation.