Regulation of Myoblast Proliferation and Differentiation
During vertebrate myogenesis, myoblast cell populations proliferate and fuse to form multinucleated muscle fibers that express a battery of contractile protein genes. The mechanisms that regulate myoblast cell proliferation versus differentiation involve extracellular signaling via growth factors, their cognate receptors, intracellular signal transduction cascades, and transcriptional regulation of genes associated with cell proliferation. Among these genes is the fibroblast growth factor receptor 1 (FGFR1) gene which is expressed in proliferating myoblasts and down-regulated during differentiation. We are interested in the transcriptional regulation of the FGFR1 gene because its expression is tightly linked to continued myoblast proliferation. Our published findings demonstrate that the FGFR1 gene is positively regulated by the Sp1 transcriptional regulator and negatively regulated by the transcription factor E2F4. The goal of our on-going research is to define and characterize the transcriptional complexes resident on the FGFR1 regulatory regions as well as those interactions off the promoter that govern its expression in both proliferating myoblasts and differentiated muscle fibers. These studies provide insight into mechanisms that regulate not only muscle cell proliferation and differentiation, but regulation of cell proliferation in general.