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.

项目总结/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 只有少数系统（果蝇中的合胞体模式，基于粘附的异质细胞分选， 种群，同质种群的梯度诱导规范）。本提案的目的是 鉴定调节成年斑马鱼色素模式形成的分子机制。成年斑马鱼 色素细胞从神经嵴来源的祖细胞分化， 细胞对于条纹图案的形成是必不可少的。其中一类色素细胞，虹彩虹膜细胞， 用于建立和重申暗条纹和亮间条纹的图案。有两种虹膜细胞亚型 在斑马鱼中：“松散的”间充质样虹膜细胞，与黑色条纹中的黑色素细胞相关， “致密的”上皮样虹膜细胞的光条纹，驱动橙子xanthophore分化内 在设置相邻条纹的位置的同时，还设置相邻条纹的位置。指定松散和密集的机制 虹膜细胞亚型尚未确定。在本提案中，目标1侧重于一个创新假设， 通过虹膜细胞、黑色素细胞和组织之间的相互作用解释亚型特化 环境涉及两个候选信号通路。目标2阐述了细胞的基本作用- 自主因素，确定了正向遗传学，在促进虹膜成熟，从而， 虹膜细胞和其他色素细胞之间的基本相互作用是图案形成的基础。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 单细胞RNA测序。这些研究将为虹膜细胞的分化和 形态发生，这将增加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。