Our research program is ultimately concerned with identifying the factors that influence epithelial cells that share a common duct, to develop in a variety of directions. We are also concerned with elucidating the cellular and molecular mechanisms leading to the specialization and function of secretory cells. The studies will be carried out using the submandibular glands of mice. It is our intention to purify and characterize several epithelial cell type-specific proteins, and to use these marker proteins to describe the course of biochemical differentiation of their respective cell types. We propose to quantitate per immunoreactive cell and measure rates of synthesis and degradation for each marker protein at different times in development. This will provide a precise analysis of the changes that are going on within the specific cell type as it differentiates. The origins of the specific cell types will be probed by cloning epithelial cells from neonatal glands and by testing the developmental potential of the clone descendants after culture with factors which have been shown to induce differentiation of different salivary gland cell-types. These experiments will help to distinguish between the possibilities that the different cell types along the duct arise from a pluri-potent stem cell line or that each type is determined individually. We have shown that two of the marker proteins, the predominant mucins from female and male glands, have different sizes and immunoreactivities. This finding suggests that there may be substantial variation in mucins from the same gland and that this variation may be hormonally induced. The extend of normal carbohydrate variation within a pure mucin, and the factors which influence it, are both questions relevant to an understanding of the mucoviscidosis component of cystic fibrosis. We propose to elucidate the basis for the biochemical and structural differences between female- and male-predominant mucins, and to explore the role of male pattern hormones in promoting this difference.