The purpose of the project is to determine the relationships between the mechanisms of action of three different classes of molecules each of which has been demonstrated to play a role in control of differentiation and/or neoplastic transformation of cells. The specific classes of molecules under investigation are: 1) polypeptide growth factors with emphasis on type alpha and beta transforming growth factors (TGFs) and platelet-derived growth factor (PDGF), each of which has been demonstrated to play a role in the maintenance of the transformed phenotype; 2) retinoids and other low-molecular weight effectors; and 3) oncogenes and their polypeptide products. Each of these classes of substances is known to affect gene expression of cells. Particular attention is directed at elucidation of the mechanism of action of the type alpha and beta TGFs in control of cell proliferation and phenotypic expression, since these polypeptides have been the focus of our laboratory's research for the past 4 years and since our laboratory is uniquely able to employ diagnostics such as receptor assays, immunoassays, and assays for messenger RNA for these peptides. Studies are aimed at three levels: in the whole embryo, in various organs and tissues, and in cell culture. Specific systems employed for these investigations include: 1) an experimental model for studying the effects of retinoids on avian embryogenesis utilizing retinoid-deficient Japanese quail embryos; 2) comparison of oncogene and TGF expression in certain tissues of retinoid-deficient compared to normal hamsters; and 3) examination of the effects of retinoids and TGFs on the expression of oncogenes by certain cultured rodent and human cell lines. Electron microscopy and in situ hybridization will be used as adjuncts to biochemical determinations in the first two systems.