Several human skin diseases, such as atopic dermatitis, psoriasis as well as regeneration processes such as wound healing are associated with epidermal barrier defects. The multi-layered epidermis is composed of proliferating basal keratinocytes that initiate upward differentiation through migration and intercalation, which ultimately lead to tight junction formation and cornification to serve as essential barriers against environmental insults and dehydration. The assembly of functional tight junctions at the interfaces of the granular layer is largely controlled by cytoskeletal rearrangements, including filamentous (F)-actin organization. However, the nature and identity of the upstream regulators of F-actin dynamics and barrier formation remain elusive. We have recently shown that STRIP1, a core component of the biochemical complex called Striatin-Interacting Phosphatase And Kinases (STRIPAK), impacts on cytoskeletal organization and cell migration in the mouse embryo. Therefore, we hypothesized that STRIP1 and the STRIPAK serve as upstream regulators of F-actin and cell-cell adhesion in the skin epidermis. To address this hypothesis, we first assessed the localization of STRIP1 in the mouse skin and showed that it distinctly decorates cell-cell junctions in the upper layers of the epidermis. Next, we functionally examined the roles of Strip1 in the skin epithelium using a conditional allele of Strip1. Only half of the K14-Cre; Strip1fl/fl mutants survived, but were significantly smaller than control animals and had broken vibrissae. Using histology and barrier assays, the Strip1 mutant skin showed misoriented hair follicles, a thinner epidermis and barrier defects. Interestingly, whole mount F-actin staining revealed wavy cell-cell borders in the granular layer of Strip1 mutants, indicating an underlying defect in mechanical tension. Collectively, the data support a model whereby STRIP1 and the STRIPAK regulate F-actin and cell-cell junctions to generate a functional barrier.

ESDR177 - The Striatin-Interacting Phosphatase And Kinases complex is important for skin epidermal differentiation and barrier formation

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.