Mechanisms of pigment cell maturation and subtype specification during zebrafish stripe pattern formation

斑马鱼条纹图案形成过程中色素细胞成熟和亚型规范的机制

• 批准号: 10413822
• 负责人: Raegan Rayfield Bostic
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413822
• 关键词: Address; Adhesions; Adult; Affect; Alleles; Appearance; Behavior; Biological Assay; Biology; Cartilage; Cell Differentiation process; Cell Lineage; Cell Maturation; Cells; Complex; Defect; Deformity; Dependence; Development; Developmental Biology; Drosophila genus; Embryo; Endothelin; Endothelin Receptor; Environment; Epithelial; Exhibits; Face; Feedback; Fibroblasts; Foundations; Future; Gene Expression Profiling; Genes; Genetic; Genetic Epistasis; Goals; Health; Heart Abnormalities; Image; In Situ; In Situ Hybridization; Individual; Intestinal Obstruction; Knock-out; Lead; Ligands; Light; Location; Melanophores; Mesenchymal; Methods; Microscopy; Molecular; Morphogenesis; Morphology; Movement; Nature; Neural Crest; Neuroglia; Neurons; Oranges; Organ; Pathway interactions; Pattern; Pattern Formation; Peptides; Peripheral; Phenotype; Pigments; Population; Positioning Attribute; Research; Resolution; Role; Signal Pathway; Signal Transduction; Skin; Skin Pigmentation; Sorting - Cell Movement; Specific qualifier value; Spottings; System; Testing; Time; Tissues; Training; Transforming Growth Factors; Transgenic Organisms; Zebrafish; base; bioinformatics tool; bone; career; cell behavior; cell type; confocal imaging; craniofacial; cysteine rich protein; deafness; experience; experimental study; forward genetics; genetic analysis; genetic manipulation; imaging modality; innovation; insight; mutant; neurodevelopment; overexpression; progenitor; self assembly; self organization; single-cell RNA sequencing; transcription factor; transcriptomics; zebrafish development

PROJECT SUMMARY/ABSTRACT There are numerous examples of self-assembled patterns in biology, but most research effort has focused on only a few systems (syncytial patterning in Drosophila, adhesion-based sorting of heterogeneous cell populations, gradient-induced specification of homogeneous populations). The goal of this proposal is to identify molecular mechanisms that regulate pigment pattern formation in adult zebrafish. Adult zebrafish pigment cells differentiate from neural crest-derived progenitors, and reciprocal interactions between pigment cells are essential for stripe pattern formation. One class of pigment cells, iridescent iridophores, is responsible for establishing and reiterating the pattern of dark stripes and light interstripes. Two iridophore subtypes occur in zebrafish: “loose,” mesenchymal-like iridophores that associate with melanophores in dark stripes, and “dense” epithelial-like iridophores of light interstripes that drive orange xanthophore differentiation within the interstripes, while also setting the positions of adjacent stripes. The mechanisms that specify loose and dense iridophore subtypes have not been determined. In this proposal, Aim 1 focuses on an innovative hypothesis to account for subtype specification via interactions among iridophores, melanophores and the tissue environment involving two candidate signaling pathways. Aim 2 addresses essential roles for a cell- autonomous factor, identified by forward genetics, in promoting iridophore maturation and, thereby, the essential interactions between iridophores and other pigment cells underlying pattern formation. Approaches will range from classical genetic analysis to time-lapse imaging, and from gene expression analysis in situ to single cell RNA-Sequencing. These studies will provide insights into iridophore differentiation and morphogenesis that will augment our understanding of the genetic basis of cellular behaviors during the dynamic self-assembly of tissue patterns.

项目摘要/摘要 生物学中有许多自组装模式的例子，但大多数研究工作都集中在 只有几个系统(果蝇的合胞体图案，基于黏附的异质细胞分选 种群，梯度诱导的同质种群规范)。这项提议的目标是 确定调节成年斑马鱼色素模式形成的分子机制。成年斑马鱼 色素细胞与神经脊祖细胞的分化以及色素之间的相互作用 细胞是条纹图案形成所必需的。有一类色素细胞--虹彩虹膜细胞--负责 用于建立和重申深色条纹和浅色条纹的图案。出现两种虹膜载体亚型 斑马鱼：“松散的”间充质样虹膜，与深色条纹的黑色素联系在一起。 “密集的”上皮样虹膜基团的光条间驱动橙色黄原基团的分化 条纹间，同时还设置相邻条纹的位置。指定松散和密集的机制 虹膜载体亚型尚未确定。在这项提议中，目标1侧重于一个创新的假设，以 通过虹膜载体、黑素载体和组织之间的相互作用来解释亚型指定 涉及两条候选信号通路的环境。目标2解决了细胞的基本角色- 自主因子，由正向遗传学确定，在促进虹膜载体成熟中，因此， 虹膜载体和其他色素细胞之间的基本相互作用，构成了图案形成的基础。方法 将从经典的遗传分析到时间推移成像，从原位基因表达分析到 单细胞RNA测序。这些研究将为虹膜载体的分化和 形态发生，这将增强我们对细胞行为的遗传基础的理解 组织图案的动态自组装。