HORMONAL CONTROL OF MUSCLE DEVELOPMENT

肌肉发育的荷尔蒙控制

• 批准号: 6179585
• 负责人: GEOFFREY E STILWELL
• 金额: $ 2.66万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6179585
• 关键词: Manduca; antisense nucleic acid; apoptosis; biological signal transduction; cell differentiation; cell proliferation; cell type; confocal scanning microscopy; developmental genetics; ecdysone; gene expression; green fluorescent proteins; hormone regulation /control mechanism; immunocytochemistry; juvenile hormones; metamorphosis; mixed tissue /cell culture; molecular cloning; myogenesis; neurons; northern blottings; polymerase chain reaction; regulatory gene; transcription factor; western blottings

In both humans and insects, hormones play a significant role in muscle development. Conditions which perturb hormone levels in mammals, such as hypo- or hyperthyroidism, disrupts muscle development and differentiation; yet, the molecular mechanisms by which steroids act to control myoblast proliferation and differentiation are not well understood. The tobacco hawkmoth M. sexta, the insect model system for endocrine control of development, will be used to explore the hormonal regulation of cell proliferation and apoptosis by ecdysteroids during myogenesis. Specifically, several ecdysteroid inducible early gene transcription factors have been identified and cloned and likely play a role in this hormonal control of cell fate. This proposal outlines experiments aimed at determining the role of the E74, Broad,and E75 early genes in muscle development during the pupal-adult transformation. Using physiology-based techniques, such as in vivo hormonal manipulations as well as a primary myocyte culture system, the role of ecdysone versus its metabolite 20-hydoxyecdysone in the control of cell proliferation, apoptosis and differentiation will be established. The identity and the timing of early gene expression will be determined in vivo and correlated with cell fate. Finally, using both anti-sense technology and transfection assays to deplete or express specific early genes, we will look at the ability of specific early genes to induce the proliferative or apoptotic cell fate.

在人类和昆虫中，激素在肌肉发育中发挥着重要作用。 扰乱哺乳动物激素水平的疾病，例如甲状腺功能减退或亢进，会破坏肌肉的发育和分化；然而，类固醇控制成肌细胞增殖和分化的分子机制尚不清楚。 烟草天蛾 M. sexta 是内分泌控制发育的昆虫模型系统，将用于探索蜕皮激素在肌发生过程中对细胞增殖和凋亡的激素调节。 具体来说，几种蜕皮类固醇诱导的早期基因转录因子已被鉴定和克隆，并且可能在细胞命运的激素控制中发挥作用。 该提案概述了旨在确定 E74、Broad 和 E75 早期基因在蛹-成虫转化过程中肌肉发育中的作用的实验。 使用基于生理学的技术，例如体内激素操作以及原代肌细胞培养系统，将确定蜕皮激素及其代谢物 20-羟基蜕皮激素在控制细胞增殖、凋亡和分化中的作用。早期基因表达的身份和时间将在体内确定并与细胞命运相关。 最后，使用反义技术和转染测定来消除或表达特定的早期基因，我们将研究特定早期基因诱导增殖或凋亡细胞命运的能力。