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

项目概要摘要 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 因损伤或疾病而损失的组织的再生对于分层组织来说尤其具有挑战性，例如 皮肤，在胚胎发育和成体再生的快速生长阶段，这里有多个细胞层。 必须有效沟通并共同成长，以确保分层不受影响。 当面临快速扩张的挑战时，细胞层的行为和协调生长需要研究 关注，但受到定量实时成像工具和平台可用性的限制。 初步研究中，我们开发了工具来可视化和操纵细胞行为和信号传导 胚胎斑马鱼表皮，以及对成年表皮进行定量实时成像的平台 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 介导的机械化学反馈在调节胚胎生长中的作用 轴向伸长过程中的表皮以及 2) 测试组织几何形状在协调表皮生长中的作用 在成年再生过程中，除鳞和角膜磨损后的皮肤的综合分析。 复杂组织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体状况。 该项目借鉴了 1) 我之前在细胞和发育生物学方面的培训，2) 实时成像技术 I 已建立对胚胎和成年斑马鱼组织进行整体成像，3）定量技能 我将在培训期间获得一组数据来分析这些数据，并且 4) 进行空间转录组学培训以定义 为了成功完成这些目标，我组装了再生过程中激活的信号通路。 指导委员会——Stefano Di Talia 博士和 Kenneth Poss 博士，他们在定量方面综合了专业知识 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，我将从我的合作者 Christoph Schmidt 博士、Terry Lechler 博士那里收到建议和意见 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促进我的发展 我有信心能够实现该项目的目标并帮助开展我的独立研究生涯。 我在获奖期间将接受的额外培训将帮助我实现建立一个 作为独立研究者的高质量研究小组