SOMATIC CELL GENETICS APPROACH TO MUSCLE DEVELOPMENT

该研究计划描述了一种体细胞遗传学方法来鉴定 在骨骼肌特异性中与MyOD协同作用的因子 转录激活。MyoD及其相关的基本螺旋-环-螺旋 蛋白质是骨骼肌分化的主开关。 关于MyoD如何在以下位置激活的具体知识缺口仍然存在 发展中的适切点及其所依据的因素 依赖于功能。这项工作的广泛长期目标是 更好地理解导致骨骼肌的转录回路 发展。这项建议的具体目的是：1.发展一种 体细胞遗传学方法在组织培养细胞基因鉴定中的应用 控制肌肉发育。2.确定平行或平行作用的因素 在肌肉分化中位于MyoD下游。3.确定因素 导致MyoD 4转录激活。进行初步研究 初步确定促进转录的单个因素的研究 MyOD的激活和细胞周期的退出。这一目标具有相关性。 对人类疾病的理解，包括肌肉营养不良和 那些因组织分化障碍而导致的先天缺陷。

The research plan describes a somatic cell genetics approach to identify factors collaborating with MyOD in skeletal muscle-specific transcriptional activation. MyoD and related basic helix-loop-helix proteins function as master switches of skeletal muscle differentiation. Specific gaps in knowledge remain pertaining to how MyoD is activated at the appropriate point in development and what factors upon which it is dependent to function. The broad long term objective of this work is to better understand the transcriptional circuitry leading to skeletal muscle development. The specific aims of this proposal are these: 1. Develop a somatic cell genetics approach in tissue culture cells to identify genes controlling muscle development. 2. Identify factors acting parallel or downstream from MyoD in muscle differentiation. 3. Identify factors leading to transcriptional activation of MyoD 4. Pursue preliminary studies tentatively identifying a single factor promoting transcriptional activation of MyOD and cell cycle withdrawal. This objective has relevance to the understanding of human disease, including muscular dystrophy and those birth defects arising from disturbances in tissue differentiation.