We are interested in elucidating the molecular mechanisms involved in skeletal muscle development. To identify and characterize extracellular regulators of skeletal muscle development, we use viral mediated gene transfer to alter gene expression in the developing chick limb. Basically, we either abrogate or augment signaling from a growth factor and assess the effects on skeletal muscle development. These studies have led to identification of FGFs as a regulator of muscle differentiation in vivo, TGFs as regulators of secondary myoblast proliferation and hedgehogs as regulators of myoblasts committed to make slow skeletal muscle fibers. We also are investigating the regulatory relationships between growth factors by inhibiting two pathways simultaneously. This is accomplished by infection with two distinct retroviruses. These methods are establishing epistatic relationships between growth factors. We are characterizing skeletal muscle stem cells and comparing these with skeletal muscle satellite cells, the cells that regenerate injured skeletal muscle tissue. Our goals are to understand the behavior of these two types of cells and their respective potential contributions to skeletal muscle regeneration. We utilize mouse genetics, a myofiber organ culture system and satellite cell lines to examine the function of satellite cells and stem cells in environments where specific growth factor signaling pathways have been abrogated or augmented. Presently, we are investigating the roles of FGF, TGF hepatocyte growth factor, and insulin-like growth factor in muscle regeneration. Our long-term goals are to understand growth and differentiation of skeletal muscle satellite and stem cells for eventual use in cell based gene therapy approaches.