EFFECTS OF MITOGENS ON MUSCLE GROWTH & GENE EXPRESSION

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The principal objective of this project is to understand, at the molecular level, two main aspects of muscle growth and development. The first set of experiments will use gene transfer technology to study the control of myoblast growth and differentiation by growth factors. The genes encoding the epidermal growth factor receptor and the basic fibroblast growth factor will be inserted and expressed in myogenic cell lines. These cells will then be tested to see if these genetic alterations cause the expected or unexpected changes in the normal program of myoblast proliferation and differentiation. Further experiments, including a molecular genetic approach to the isolation of the fibroblast growth factor receptor, will be done to elucidate the mechanism of growth factor activity in a differentiation cell system. A second set of experiments will be done using, subtraction cDNA cloning technology, to identify and isolate myoblast genes which are regulated during the determination and proliferation stages of muscle development. Genes which are expressed in response to fibroblast growth factor stimulated proliferation will be cloned. These genes will be characterized to identify proteins which are required during the proliferative stage of myogenesis and to further understand the mechanism of growth factor response. The genes which are activated during the commitment of embryonic cells to the myoblast lineage will also be isolated. These genes will provide the initial characterization of the changes in genetic activity during the period of cell fate determination and the factors controlling this poorly understood stage of development.