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， 骨骼肌特异性MyOD的协同因素 转录激活MyoD和相关的碱性螺旋-环-螺旋 蛋白质充当骨骼肌分化的主开关。 关于MyoD如何被激活， 发展的适当点以及它所依赖的因素 依赖于功能。这项工作的长期目标是 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标是：1.开发一个 体细胞遗传学方法在组织培养细胞中鉴定基因 控制肌肉发育。2.确定平行作用的因素， 在肌肉分化中位于MyoD的下游。3.确定因素 导致MyoD 4的转录激活。进行初步调查 初步确定一个促进转录的单一因子的研究 MyOD激活和细胞周期退出。这一目标具有相关性 对人类疾病的理解，包括肌肉萎缩症， 由组织分化障碍引起的出生缺陷。

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.