Mechanism of epidermal coordination during development and regeneration in zebrafish

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PROJECT SUMMARY ABSTRACT Coordination of cell behaviors is essential for growth in embryonic and juvenile animals, as well as during regeneration of tissue lost by damage or disease. This is particularly challenging for stratified tissues, such as skin, during rapid phases of growth in embryonic development and adult regeneration. Here, multiple cell layers would have to communicate effectively and grow together to ensure stratification remains unaffected. How skin cell layers behave and coordinate their growth when challenged with rapid expansion requires research attention but has been limited by the availability of tools and platforms for quantitative live imaging. In preliminary studies, we have developed tools to visualize and manipulate cell behaviors and signaling in embryonic zebrafish epidermis, as well as a platform to perform quantitative live imaging of adult epidermis during regeneration. To understand the mechanism of coordination between epidermal layers, we will: 1) test the role of tissue tension and MAPK mediated mechanochemical feedback in regulating growth of embryonic epidermis during axial elongation and 2) test the role of tissue geometry in coordinating epidermis growth during adult regeneration following scale plucking and corneal abrasion. This comprehensive analysis of skin growth during development and regeneration of complex tissues will inform strategies for control of repair in human conditions of tissue damage or disease. The project draws on 1) my previous training in cell and developmental biology, 2) live imaging technique I have established to perform in toto imaging of embryonic and adult zebrafish tissues, 3) the quantitative skill set I will acquire during my training to analyze this data and 4) training on spatial transcriptomics to define signaling pathways activated during regeneration. For successful completion of these aims, I have assembled a mentoring committee – Dr. Stefano Di Talia and Dr. Kenneth Poss, whose combined expertise in quantitative biology, zebrafish genetics and regeneration biology will train me to become an expert on these topics. In addition, the advice and input I will receive from my collaborators – Dr. Christoph Schmidt, Dr. Terry Lechler and Dr. Brigid Hogan - on tissue mechanics, epithelial and skin biology and career development will further my ability to achieve the goals of this project and help launch my independent research career. I am confident that the additional training I will receive during this award will help me achieve my long-term goal of establishing a high-quality research group as an independent investigator