Mechanism of epidermal coordination during development and regeneration in zebrafish

项目摘要 细胞行为的协调对于胚胎和幼年动物的生长以及发育过程中至关重要。 因损伤或疾病而失去的组织的再生。这对于分层组织尤其具有挑战性，例如 皮肤，在胚胎发育和成体再生的快速生长阶段。在这里，多个细胞层 必须进行有效沟通，共同成长，以确保不受分层影响。皮肤如何 细胞层的行为和协调他们的增长时，挑战与快速扩张需要研究 但是受到定量实时成像工具和平台可用性的限制。在 初步研究，我们已经开发出可视化和操纵细胞行为和信号的工具， 胚胎斑马鱼表皮，以及一个平台，以执行定量活成像成人表皮 在再生过程中。为了了解表皮层之间的协调机制，我们将：1）测试 组织张力和MAPK介导机械化学反馈在调控胚胎生长中作用 2）测试组织几何形状在协调表皮生长中的作用 在拔鳞和角膜擦伤后的成体再生过程中。皮肤的全面分析 在复杂组织的发育和再生过程中的生长将为控制修复的策略提供信息， 组织损伤或疾病的人类状况。 该项目借鉴了1）我以前在细胞和发育生物学方面的培训，2）实时成像技术， 已经建立了对胚胎和成年斑马鱼组织进行全面成像的技术，3）定量技术 我将在培训中获得一组数据来分析这些数据，4）空间转录组学培训来定义 再生过程中激活的信号通路。为了成功地实现这些目标，我召集了 一个指导委员会-Stefano Di Talia博士和Kenneth Poss博士，他们在定量研究方面的综合专长 生物学、斑马鱼遗传学和再生生物学将训练我成为这些主题的专家。在 此外，我将从我的合作者那里得到的建议和投入-Christoph施密特博士，Terry Lechler博士 和布里吉德霍根博士-对组织力学，上皮和皮肤生物学和职业发展将进一步我 有能力实现这个项目的目标，并帮助启动我的独立研究生涯。我深信 我在此期间将接受的额外培训将帮助我实现建立一个 作为独立调查员的高质量研究小组

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