The two major cell types that form the nervous system are neurons and glial cells. Genesis of glial and neuronal cells, their differentiation and maturation in developing nervous system are thought to be controlled by proteins (growth factors) expressed at individual developmental stages. Controlled expression of growth factors may also underlie the plasticity that occurs in the adult nervous system during learning or regeneration of nervous tissue (stimulation of cells). Aberrant expression of growth factors has been implicated in the transformation of normal glial cells to tumorigenic glioma cells. Hence, to understand development, adult plasticity of the nervous tissue, and tumorigenic transformation it is essential to elucidate mechanisms that control expression of genes encoding growth factor proteins. One such protein is basic fibroblast growth factor (bFGF). Elucidation of the mechanisms controlling expression of the gene that encodes the bFGF protein is of the highest priority. Very little is known about regulation of this protein which is critical for neural and glial development and plasticity. The PI's have revealed that expression of the BFGF gene is transiently increased during reversible transition of quiescent (nondividing) glial cells to reactive (actively dividing) glia. Such reversible activation of glia is thought to play a role in neural development and in the support of adult neural plasticity. The PI has also shown that expression of the bFGF gene is permanently increased in irreversibly transformed tumorigenic glioma cells. In both cases increased expression of bFGF gene was responsible for the changes in the biology of glia (transient and permanent induction of cell proliferation). The overall aim of this project is to determine the molecular mechanisms underlying the above-mentioned changes in bFGF gene expression. The analysis of the bFGF gene has indicated that there are fundamental differences in the mechanisms by which t his gene is regulated as compared to other genes, and that novel mechanisms are involved in the regulation of bFGF gene. Identification of those mechanisms will lead to a better understanding of the molecular events controlling the biology of glial cells in the developing and adult nervous system.
