SPECIFICATION OF FAST AND SLOW MUSCLES IN ZEBRAFISH

斑马鱼快肌和慢肌的规格

• 批准号: 6490213
• 负责人: Shaojun Du
• 金额: $ 16.66万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6490213
• 关键词: alternatives to animals in research; cell differentiation; cell population study; cell type; complementary DNA; developmental genetics; gene expression; in situ hybridization; molecular cloning; muscle cells; myogenesis; nonmammalian vertebrate embryology; posttranslational modifications; zebrafish

DESCRIPTION (adapted from investigator's abstract): Vertebrate skeletal muscles are composed of two major populations of cells, slow muscle cells and fast muscle cells. These cells with their specific functions and pattern of gene expression, have become a popular system for studying mechanisms that underlie determination of cell fate. Recent studies have demonstrated that slow and fast muscle is regulated by Hedgehog secreted by the notochord, and bone morphogenetic proteins (BMPs) secreted by ectoderm cells. Hedgehogs and BMPs impose their patterning activities on responsive cells via transcription factors, that in turn regulating differentiation programs in responsive cells. Many genetic studies have implicated Glis in transducing HH and BMP signals. Several members of the Gli family are expressed in somites of Xenopus, chick, mouse and zebrafish embryos. Recent genetic studies in zebrafish have shown that a mutation in Gli2 causes a defect in slow muscle formation. The investigators have recently isolated a full length Gli4 from zebrafish. Preliminary data have shown that Gli4 is strongly expressed in paraxial mesoderm and developing somites. They hypothesize that members of the Gli family of transcription factors regulate differentiation of slow and fast muscle cell lineages in zebrafish, and that the expression of individual Glis and their ability to activate or inhibit transcription of responsive genes is controlled by Hedgehogs and BMPs. The regulation of Gli activity may occur at transcriptional, translational and/or posttranslational level (proteolysis). The specific aim of this proposal is to investigate the expression, function and regulation of Gli4 in the differentiation of muscle cells in zebrafish embryos. The long-term goal of this study is to elucidate the molecular mechanisms behind determination of muscle-specific cell fate during embryonic development.

描述（改编自研究者摘要）：脊椎动物骨骼肌 由两种主要的细胞群组成，慢肌细胞和快肌细胞。 肌肉细胞这些细胞具有特定的功能和基因模式， 表达，已经成为一个流行的系统，用于研究机制， 决定细胞命运。最近的研究表明，缓慢和快速 肌肉由脊索分泌的Hedgehog调节，骨 由外胚层细胞分泌的形态发生蛋白（BMP）。刺猬和BMP 通过转录将它们的图案化活性强加于应答细胞 这些因子反过来调节应答细胞的分化程序。 许多遗传学研究表明，Glis参与了HH和BMP信号的转导。 Gli家族的几个成员在非洲爪蟾，小鸡， 小鼠和斑马鱼胚胎。最近对斑马鱼的遗传学研究表明， Gli 2的突变导致了缓慢肌肉形成的缺陷。的 研究人员最近从斑马鱼中分离出了全长Gli 4。 初步数据显示，Gli 4在近轴区强烈表达， 中胚层和发育体节。他们假设格利人的成员 转录因子家族调节慢分化和快分化 斑马鱼肌肉细胞谱系，以及单个Glis的表达， 它们激活或抑制应答基因转录的能力， 由刺猬和BMP控制Gli活性的调节可能发生在 转录、翻译和/或翻译后水平（蛋白水解）。 本建议的具体目的是研究表达，功能 Gli 4在斑马鱼肌细胞分化中的作用及调控 胚胎本研究的长期目标是阐明 胚胎发育过程中肌肉特异性细胞命运的决定机制 发展