The interaction of growth factors with target cells triggers a cascade of cellular events: receptor-ligand binding, internalization of the receptor-ligand complex, changes in transmembrane ionic fluxes, release of second messengers, diffferential gene expression, and a specific biological response. Our work has focused on the early gene responses of cells to mitogenic and differentiative stimuli. It is the purpose of these studies to further dissect and compare the cellular pathways involved in cell proliferation and differentiation. Phase I will consist of three parts: (i) an investigation of the interrelationships between early changes in ionic fluxes and gene expression, (ii) a study of early gene expression in neuronal cells in primary culture, and (iii) a search for genes specific for cell differentiation. Phase II will employ the techniques used in Phase I to study the cellular control mechanisms in renal cell hypertrophy. We hope to isolate and characterize hypertrophy- specific genes with the aim of studying their role in compensatory renal hypertrophy and the renal hypertrophy of diabetes mellitus.