The Disintegrin/Metalloproteinase Adam10 Is Essential for Epidermal Integrity and Notch-Mediated Signaling

The study investigated the role of the enzyme Adam10 in skin development and maintenance by selectively disrupting its function in the epidermis. The deletion of Adam10 during skin morphogenesis using K14-Cre led to perinatal lethality, compromised skin barrier, and the absence of sebaceous glands. Additionally, there was a reduction in the number of spinous layers without changes in cell proliferation or apoptosis, suggesting premature differentiation of keratinocytes. Some mice with Adam10 deletion survived but exhibited hair loss, malformed vibrissae, epidermal hyperproliferation, cyst formation, thymic atrophy, and increased levels of the cytokine TSLP, indicating a multi-organ disease due to a compromised barrier. These symptoms are similar to those seen in Notch signaling pathway deficiencies. The study found that Notch processing was significantly reduced, leading to decreased levels of Notch intracellular domain fragment and functional Notch signaling. The results demonstrate that Adam10 is essential for Notch processing in the epidermis and is a key regulator of skin integrity and function.