Mechanism of epidermal coordination during development and regeneration in zebrafish

斑马鱼发育和再生过程中表皮协调机制

• 批准号: 10643060
• 负责人: Nitya Ramkumar
• 金额: $ 10.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643060
• 关键词: Address; Adopted; Adult; Animals; Anterior; Area; Attention; Automobile Driving; Award; Behavior; Biological Models; Biology; Cell Proliferation; Cell Shape; Cell division; Cells; Cellular biology; Communication; Complex; Cornea; Corneal Abrasion; Couples; Data; Desmosomes; Development; Developmental Biology; Disease; Embryo; Embryonic Development; Ensure; Epidermis; Epithelium; Equilibrium; Etiology; Feedback; Fertilization; Genetic; Geometry; Goals; Growth; Human; Image; Imaging Techniques; Injury; MAP Kinase Gene; MAPK Signaling Pathway Pathway; Measures; Mechanics; Mediating; Mentors; Modeling; Natural regeneration; Pathway interactions; Periderm; Phase; Proliferating; Research; Research Personnel; Role; Shapes; Signal Pathway; Signal Transduction; Skin; Stratification; Stratified Epithelium; Stratum Basale; Surface; System; Testing; Time; Tissues; Training; Transgenic Organisms; Visualization; Work; Zebrafish; career; career development; cell behavior; corneal regeneration; experience; experimental study; human disease; juvenile animal; mechanotransduction; novel; novel therapeutic intervention; optogenetics; regenerative biology; repaired; sensor; skills; skin regeneration; stem cell proliferation; stem cells; tissue regeneration; tool; transcriptomics

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

项目摘要摘要 细胞行为的协调对于胚胎和青少年动物的生长以及在 因损害或疾病而失去的组织的再生。对于分层组织，例如 皮肤，在胚胎发育和成人再生中生长的快速阶段。在这里，多个小区层 必须有效地交流并共同成长，以确保分层不受影响。皮肤如何 在挑战快速扩张时，细胞层的行为并协调其增长需要研究 注意，但受到定量实时成像的工具和平台的可用性的限制。在 初步研究，我们开发了可视化和操纵细胞行为和信号传导的工具 胚胎斑马鱼表皮，以及进行成人表皮定量实时成像的平台 在再生期间。要了解表皮层之间协调的机制，我们将：1）测试 组织张力和MAPK介导的机械化学反馈在恢复胚胎生长中的作用 轴向伸长期间表皮和2）测试组织几何学在配位表皮生长中的作用 在成人再生期间，尺度毛绒和角膜磨损。对皮肤的全面分析 复杂组织的开发和再生期间的增长将为控制维修的策略提供信息 人类组织损伤或疾病的状况。 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）实时成像技术i 已经建立了在胚胎和成年斑马鱼组织的toto成像中执行的，3）定量技能 设置我将在培训期间获得分析此数据和4）关于空间转录组学的培训以定义 在再生过程中激活的信号通路。为了成功完成这些目标，我已经组装了 心理委员会 - Stefano di Talia博士和Kenneth Poss博士，其定量方面的综合专业知识 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。 此外，我将从合作者克里斯托夫·施密特（Christoph Schmidt）博士特里·莱希勒（Terry Lechler）博士那里收到的建议和意见 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进一步进一步 能够实现该项目的目标并帮助启动我的独立研究职业。我有信心 在此奖励期间我将接受的额外培训将有助于我实现建立一个长期目标 高质量的研究小组作为独立研究者