Understanding the organization and functional expression of dental structural genes during human development may be helpful in formulating new diagnostic and therapeutic approaches for a number of oral diseases affecting enamel, dentine, cementum and related dental tissues. Our research program represents an interdisciplinary and multidisciplinary approach to the investigation of enamel, dentine and cementum structural genes and their products during mouse and human development. Our efforts are integrated towards understanding the molecular genetics of amelogenesis, dentinogenesis and cementogenesis. We propose to identify and characterize the structural organization of the major genes and their products associated with enamel, dentine and cementum formation in normal as well as within affected individuals expressing inherited disorders of enamel, dentine and cementum. Our experimental strategy is to identify and characterize unique proteins characteristic of enamel, dentine and cementum, and to use these polypeptides as immunogens to produce monospecific polyclonal antibodies. These antibodies are then used to identify putative antigenic cross-reactivity between mouse and human dental proteins. These antibodies are also used to characterize specific mRNAs for each of the dental non-collagenous extracellular matrix structural gene products, which are then used to produce complementary DNA probes (cDNA). Recombinant DNA techniques are employed in studies designed to determine putative homology between mice and human genomic DNA containing structural genes of enamelins, amelogenins, dentine phosphoprotein and intermediate cementum non-collagenous protein. We propose to investigate families consisting of normal and affected individuals clinically diagnosed as having one of the dental genetic diseases such as amelogenesis imperfecta (AI) or dentinogenesis imperfecta (DI). These studies will result in a detailed analysis of each of these human dental structural genes and may establish the molecular pathology for a number of inherited disorders of dental tissues.