Mechanism of epidermal coordination during development and regeneration in zebrafish

项目总结摘要 细胞行为的协调对于胚胎和幼年动物的生长以及在 再生因损伤或疾病而失去的组织的再生这对于层状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，多个单元层 必须有效沟通并共同发展，以确保分层不受影响。如何蒙皮 细胞层在面临快速扩展的挑战时表现并协调其生长需要研究 但是，定量实时成像的工具和平台的可获得性限制了这一点。在……里面 初步研究，我们已经开发了工具来可视化和操纵细胞行为和信号转导 斑马鱼胚胎表皮，以及对成体表皮进行定量实时成像的平台 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介导的机械力化学反馈在调节胚胎生长中的作用 2)测试组织几何形状在协调表皮生长中的作用 在鳞片拔除和角膜擦伤后的成人再生过程中。这是对皮肤的全面分析 复杂组织发育和再生过程中的生长将提供控制修复的策略 人体组织受损或疾病的状况。 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)活体成像技术 已经建立了对胚胎和成年斑马鱼组织进行整体成像的能力，3)定量技能 我将在我的培训期间获得SET来分析这些数据，以及4)关于空间转录的培训，以定义 信号通路在再生过程中被激活。为了成功地实现这些目标，我召集了 指导委员会-Stefano Di Talia博士和Kenneth Poss博士，他们在量化方面的综合专长 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……里面 此外，我将从我的合作者-Christoph Schmidt博士、Terry Lechler博士那里获得建议和意见 和Brigid Hogan博士-关于组织力学、上皮和皮肤生物学以及职业发展将促进我的 有能力实现这个项目的目标，并帮助我开始独立的研究事业。我相信 在这个奖项期间，我将接受额外的培训，这将帮助我实现建立一个 作为独立调查者的高质量研究小组

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