Notch signalling plays a crucial role in the development and maintenance of the epidermis: the stratified epithelium that forms the skin's outer layer and protects organisms from dehydration, mechanical trauma and microbial invasion. Now, on , Carien Niessen, Paul Saftig and colleagues reveal that the disintegrin/metalloproteinase Adam10, a `sheddase' involved in Notch processing, is essential for epidermal integrity and Notch-mediated epidermal signalling in mice. The researchers show that epidermal-specific deletion of Adam10 in mouse embryos leads to perinatal death, impairment of the skin's barrier function and an absence of sebaceous glands. Moreover, deletion of Adam10 in adult mice causes hair loss, epidermal hyperproliferation and cyst formation. These phenotypes closely resemble those produced by epidermal inactivation of Notch signalling. Indeed, the researchers report that epidermal loss of Adam10 severely impairs Notch processing and signalling in the epidermis. Together, these data identify Adam10 as the major Notch processing enzyme in the epidermis in vivo and as a central regulator of skin development and maintenance.
