Post-embryonic neural crest-derived progenitors in zebrafish during development and maintenance of adult phenotypes

项目摘要/摘要 胚胎中的细胞命运程序越来越为人所知，但对那些调节细胞命运的程序知之甚少 胚胎后发育。然而，这样的程序对于成体表型的形成是必不可少的。 随着动物的生长和发育，永续祖细胞分化产生新的组织或 有助于在幼虫阶段启动的模式的扩展。这些胚胎后的祖细胞 人口没有得到很好的研究，而有重点的检查对于我们努力理解成年人是如何 表型出现了。 神经脊(NC)是脊椎动物特有的胚胎细胞群体，它能产生 各种各样的细胞类型。它已被证明是研究细胞谱系和 细胞命运的动态控制。鉴于许多关于NC和NC细胞在其中的作用的知识 胚胎发生，来自NC的胚胎后祖细胞的研究要少得多。之前的工作 斑马鱼已经表明，胚胎后NC衍生的祖细胞分化为各种类型的细胞，包括 色素细胞和神经胶质细胞。关于这些细胞的悬而未决的问题涉及它们的解剖利基，它们的范围 发育过程中的命运以及这些命运是如何被指定的，以及它们的正常作用和分化潜力 在成人中，特别是在再生的背景下。 为了解决这些问题，我设计了一系列斑马鱼实验。在目标1中，我将调查 NC来源的祖细胞(NCP)在仔鱼到幼鱼中的作用，主要集中在鉴定它们的解剖学上 地点(S)和命运(S)。这项工作将涉及对单细胞表达数据进行解剖映射以定位 先祖细胞群体的假定生态位，以及体内单细胞命运图谱。在《目标2》中，我会 研究NCPs在维持成体形态中的作用以及这些细胞在 利用命运图谱和单细胞转录转录技术进行再生。建议的分析将扩大我们的 胚胎后NC衍生细胞中细胞命运程序的知识，并将支持未来的干细胞研究 细胞治疗学和再生医学。

PROJECT SUMMARY/ABSTRACT Cell fate programs in the embryo are increasingly well understood, but little is known about those that mediate post-embryonic development. Nevertheless, such programs are essential to the formation of adult phenotypes. As an animal grows and develops, persisting progenitor cells differentiate to produce new tissues or to contribute to the expansion of patterns initiated in the larval stages. These post-embryonic progenitor populations are not well studied, and a focused examination is critical in our efforts to understand how adult phenotypes arise. The neural crest (NC) is an embryonic population of cells uniquely present in vertebrates that gives rise to a diverse range of cell types. It has proven to be an exceptional model system for investigating cell lineage and the dynamic controls of cell fate. Whereas much is known about the NC and the roles of NC cells in embryogenesis, post-embryonic progenitor cells derived from the NC have been far less studied. Prior work in zebrafish has shown that post-embryonic NC-derived progenitors differentiate into various cell types including pigment cells and glia. Outstanding questions about these cells concern their anatomical niches, their range of fates during development and how these fates are specified, and their normal roles and differentiative potential in adults, particularly in the context of regeneration. To address these issues, I have devised a series of experiments in zebrafish. In Aim 1, I will investigate the role of NC-derived progenitors (NCPs) in larva-to-juvenile fish, focusing primarily on identifying their anatomical location(s) and fate(s). This work will involve mapping single-cell expression data anatomically to locate presumptive niches of progenitor populations, as well as single-cell fate mapping in vivo. In Aim 2, I will examine the role of NCPs in maintenance of the adult form and the potential of these cells in the context of regeneration using fate mapping and single-cell transcriptomics. The proposed analyses will expand our knowledge of cell fate programs in post-embryonic NC-derived cells and will support future research in stem cell therapeutics and regenerative medicine.