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，但是大多数研究工作都集中在 只有少数系统（果蝇中的合成图案，基于粘合剂的异质细胞排序 人群，梯度引起的同质种群的规范）。该提议的目的是 确定在成年斑马鱼中调节色素模式形成的分子机制。成人斑马鱼 色素细胞与神经波峰衍生的祖细胞区分开，色素之间的相互作用 细胞对于条纹模式形成至关重要。一类色素细胞，虹膜虹膜粒子，是负责的 出现了两种虹膜亚型，以建立和重申暗条纹和光线间的模式。 在斑马鱼中：“松散”，类似于黑色条纹的黑色素粒子的间充质状虹膜液和 “密集”的上皮样虹膜粒子的光线间，使橙色的黄蜂分化在 间隔，同时还设置了相邻条纹的位置。指定松散且致密的机制 虹膜亚型尚未确定。在此提案中，目标1专注于创新的假设 通过虹膜，黑色素和组织之间的相互作用来解释亚型规范 涉及两个候选信号通路的环境。 AIM 2解决了细胞的重要作用 自主因素，通过正向遗传学确定，促进虹膜化的成熟，从而 虹膜载体与其他色素细胞之间的基本相互作用。方法 从经典的遗传分析到延时成像，从原位基因表达分析到原位 单细胞RNA序列。这些研究将为虹膜分化和 形态发生，将增强我们对细胞行为遗传基础的理解 组织模式的动态自组装。