Regulation of Eye Regrowth in Xenopus laevmis

非洲爪蟾眼睛再生的调节

• 批准号: 10665760
• 负责人: Kelly Tseng
• 金额: $ 18.69万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665760
• 关键词: Ablation; Adult; Age; Animals; Biological Assay; Biology; Biomedical Research; Cell Compartmentation; Cell Cycle; Cell Maintenance; Cell membrane; Compensation; Data; Dependence; Development; Developmental Biology; Dimensions; Disease; Drosophila genus; Embryo; Embryonic Development; Embryonic Eye; Environment; Event; Excision; Exhibits; Eye; Eye Development; Eye Injuries; Failure; Foundations; Gene Expression; Generations; Genes; Genetic Epistasis; Goals; Growth; Growth and Development function; Histologic; Human; Injury; Knowledge; Left; Link; Location; Maintenance; Membrane; Methods; Microsurgery; Minority-Serving Institution; Modeling; Mus; Natural regeneration; Neuronal Differentiation; Operative Surgical Procedures; Organ; Organelles; Pathway interactions; Pattern; Plasma; Process; Productivity; Protocols documentation; Proton Pump; Proton-Translocating ATPases; Rana; Regulation; Research; Role; Sagittaria; Signal Pathway; Signal Transduction; Site; Structure; Study models; System; Tadpoles; Tail; Testing; Time; Tissues; Transcript; Vision; Visual Fields; Xenopus; Xenopus laevis; Yeasts; Zebrafish; bioelectricity; cell type; eye formation; gain of function; in vivo; insight; interest; limb regeneration; loss of function; minority student; nerve stem cell; notch protein; novel; organ regeneration; programs; regenerative; regenerative biology; regenerative repair; repair strategy; repaired; retinal progenitor cell; retinal regeneration; spatiotemporal; stem cell proliferation; stem cells; student participation; tissue repair; voltage

PROJECT SUMMARY A main challenge in the regeneration field has been to identify the signaling pathways and suitable cell types needed to enable productive tissue repair. For the eye, the successful generation and maintenance of eye-specific stem cells is a key goal. Although the process of vertebrate eye development is well-studied and characterized, the mechanisms that can induce eye stem cell proliferation following injury or disease remain difficult to identify. This is partly because natural stem cell proliferation typically occurs during embryo development whereas studies of retinal regeneration have largely utilized adult (or mature) models – a very different environment. The highly regenerative clawed frog, Xenopus laevis, is an established model for both development and organ regeneration. It is also closely related to humans. We found that Xenopus embryos successfully regrew functional eyes within 5 days. Our studies also showed that successful eye regrowth required increased and extended retinal stem cell proliferation while delaying new eye formation. One candidate pathway to regulate eye regrowth is bioelectrical signaling. Bioelectrical signaling is well-characterized for its role in limb regeneration but its role in eye development and regrowth is unclear. Our data showed that inhibition of bioelectrical signaling blocked eye regrowth, indicating that its function is required. We seek to understand and define the roles of bioelectrical signaling during eye regrowth, as a first step towards establishing a protocol for effectively dissecting the similarities and distinctions between development and repair. This project will: 1) define the expression patterns and key function of bioelectrical signaling components during eye regrowth and development; 2) assess the role of bioelectrical signaling in activating regenerative retinal progenitor cell proliferation and expansion, and 3) identify potential downstream targets. Together, this proposal will leverage the unique biology of Xenopus to establish an efficient strategy to rapidly define key mechanisms that regulate regrowth-induced retinal progenitor cell proliferation in vivo. This protocol will set the foundation for eventually building a blueprint for productive eye repair strategies.

项目摘要 再生场的主要挑战是确定信号通路和合适的 实现产品组织修复所需的细胞类型。对于眼睛，成功的一代和 维护眼睛特异性干细胞是一个关键目标。虽然脊椎动物眼发育的过程是 经过充分研究和表征，可能在受伤后引起眼科干细胞增殖的机制 或疾病仍然难以识别。这部分是因为天然干细胞增殖通常发生 在胚胎发育过程中，对视网膜再生的研究在很大程度上使用了成人（或成熟） 模型 - 一个非常不同的环境。高度再生的爪蛙Xenopus laevis是一个 开发和器官再生的既定模型。它也与人类密切相关。我们 发现Xenopus胚胎在5天内成功地重新起了功能性眼睛。我们的研究也表明 成功的眼睛遗憾需要增加和扩展残留的干细胞增殖，同时延迟 新的眼睛形成。一种调节眼睛调节的候选途径是生物电信信号传导。生物选择 信号传导因其在肢体再生中的作用而被充分表现，但在眼睛发育和改革中的作用 不清楚。我们的数据表明，抑制生物信号传导阻碍了眼睛的改革，表明其 需要功能。我们寻求理解和定义眼睛期间生物电信的作用 遗憾的是，作为建立有效剖析相似性和的协议的第一步 开发与维修之间的区别。该项目将：1）定义表达模式和键 眼睛改革和发育过程中生物电信机成分的功能； 2）评估角色 在激活再生视网膜祖细胞增殖和膨胀时，生物电信号传导，3） 确定潜在的下游目标。该提议在一起将利用Xenopus的独特生物学来 建立有效的策略，以快速定义调节受调节诱导的视网膜的关键机制 体内祖细胞增殖。该协议将为最终建立一个蓝图奠定基础 生产性眼睛修复策略。