SOMATIC CELL GENETICS APPROACH TO MUSCLE DEVELOPMENT

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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.