Novel Nuclear Signaling Mechanisms in Control of FGF-2 Expression in Astrocytes

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9728923 STACHOWIAK The two major cell types that form the nervous system are neurons and glia. Genesis of glial and neuronal cells, and their differentiation and maturation in the developing nervous system are thought to be controlled by proteins (growth factors) expressed at specific developmental stages. Controlled expression of growth factors may also underlie plasticity that occurs in the adult nervous system during learning or regeneration of nervous tissue (stimulation of cell division, changes in cell shape and in contacts between 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 nervous system tissue, and tumorigenic transformation it is essential to elucidate mechanisms that control expression and function of growth factor proteins. Basic fibroblast growth factor (bFGF or FGF-2) is one such protein that is critical for neuronal and glial development, plasticity, and tumorigenic transformation. Elucidation of the mechanism controlling bFGF expression and function is of the highest priority. Studies in Dr. Stachowiak's laboratory have revealed that expression of bFGF is transiently increased during the shift of quiescent (non-dividing) glial cells to reactive (actively dividing) glia. Such reversible activation of glia plays an important role in neural development and in the support of adult neural plasticity. Dr. Stachowiak's laboratory has also shown that the expression of the bFGF gene is permanently increased in irreversibly activated tumorigenic glia (glioma tumors). The overall aim of this project is to determine the molecular mechanisms underlying the above-mentioned changes in bFGF gene expression. The investigation has indicated that there are fundamental differences in the mechanisms by which the bFGF gene is regulated as compared to other genes. Identification of those mechanism will lead to a better understanding of the molecular-genetic control of the development and plasticity of the nervous system.