One of the reasons that the study of development of submandibular gland is intriguing is because it raises the question of how do several secretory cell types arise on a contiguous duct. Additionally, the potential for changing the proportions of these ductal secretory cells is retained throughout adulthood. This latter phenomenon suggesting that upon further understanding of the process, directed salivary gland regeneration may be possible in the future. This proposal will address several questions in the sequence of submandibular gland development that will benefit from the level of sensitivity and precision of identification that can only be achieved through radioimmunoassay of cell type-specific proteins. The fate of an early secretory cell type, terminal tubule cell, will be investigated along with the mechanism of disappearance of the major protein produced in neonatal submandibular gland. The stages in the differentiation of the acinar cell will be investigated by way of its specific mucin. Procedures are outlined for quantitating the total mucin in a gland and the amount of mucin per acinar cell at any stage of development. The rates of synthesis will be obtained. It is also proposed to produce cell clones of neonatal and adult epithelial-like cells and to test the developmental potential of the clone cells by treatment with development-inducing drugs such as isoproterenol and testosterone. This approach is designed to explore the possibility that a stem cell which may be carried into adulthood has the potential to give rise to both of the major secretory cell types of the adult gland. Salivary mucins have a broad role in maintaining a healthy environment in the oral cavity, providing lubrication, moisturization, protection and facilitating removal of particulates including oral microbes. It is thought that the carbohydrate composition of the mucins is the key to their many functions. Can mucins adapt to the needs of the oral cavity with changes in the carbohydrate composition? Are they modified by chronic diseases or their treatments? Do they change as development progresses? These questions are specifically addressed in mice using the submandibular mucin. A method is described and its feasibility is demonstrated for obtaining the carbohydrate composition of the mucin from one gland. The steps for oligosaccharide structural composition are also presented. These analyses will be performed on mucins from different stages of development and following chronic treatment with different drugs.
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