Hemidesmosomes And Notch Signaling Regulate Epidermal Differentiation Via Delamination

The study investigates the role of hemidesmosomes and Notch signaling in epidermal differentiation through delamination. Using a lentiviral-mediated approach, researchers generated mosaic, epidermal-specific loss of integrin-β4 or its ligand, laminin-α3β3ɣ2, in mice. Despite known postnatal skin blistering from mutations in these genes, no embryonic epidermal-dermal separation was observed. However, loss of these components led to increased delamination of basal keratinocytes into the suprabasal layer. Hyperactive Notch signaling decreased integrin-β4 expression and increased delamination, while deletion of the Notch effector Rbpj had the opposite effect. These findings highlight hemidesmosomes' role in regulating epidermal differentiation through mitotic and non-mitotic mechanisms.