The STRIPAK complex in skin epidermal differentiation and barrier formation

• Applicant: Dr. Hisham Bazzi, Ph.D.
• Subject Area: Developmental Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491326730

How epithelial cells reorganize their cytoskeleton and remodel their adhesive junctions during migration and intercalation are fundamental open questions in animal biology. In particular, the upstream regulators of cytoskeletal dynamics during these processes are not well understood. We have recently shown that Striatin-Interacting Protein 1 (STRIP1), a core component of the Striatin-Interacting Phosphatases And Kinases (STRIPAK) complex that regulates PP2A phosphatase activity, is essential for actin organization to facilitate cellular migration and convergent extension rearrangements during mouse gastrulation. However, the mechanism linking STRIP1 and the STRIPAK to cytoskeletal dynamics remains unresolved. In this application, we will address this question using the developing mouse skin epidermis as a biologically highly relevant model tissue. The epidermis undergoes stereotypical cellular rearrangements during differentiation to ultimately provide the skin barrier. Our preliminary data show that STRIP1 is localized at cell-cell adhesion junctions in the granular suprabasal layer of the epidermis and is required for the formation of an intact barrier. Based on our findings, we hypothesize that STRIP1 is required to integrate the functions of the STRIPAK to modulate actomyosin activity and stabilize cell-cell adhesion for proper barrier formation. To address this hypothesis, we propose an experimental plan combining in vivo mouse genetics and cutting-edge imaging with in vitro cell and mechanobiology. Our work will contribute to our understanding of how cytoskeletal organization is regulated by upstream biochemical complexes, e.g. the STRIPAK, and impact cell adhesion and cellular differentiation to ensure tissue morphogenesis and epithelial barrier function.

• DFG Programme: Research Grants