The long-term objective of this research is an understanding of the processes involved in regeneration of periodontal ligament attachment to tooth root surfaces. Towards this goal it is proposed to investigate the biological mechanisms involved in root development. The isolation of the epithelial root sheath (ERS) from developing mandibular first molars of mice has made it possible to examine a number of hypotheses related to the role of tissue interactions in root development. The inductive capabilities of ERS cells in the formation of root dentin will be determined using tissue separation and recombination techniques. The distribution of laminin, fibronectin, types I, III, IV collagen and changes in their distribution during cellular differentiation will be examined using antibodies directed against these molecules. The potential contribution of ERS cells, in the form of enamel proteins, to the first-formed matrix of the root will be investigated using monoclonal antibodies raised against amelogenins; and the inductive capabilities of ERS and this first-formed matrix in the formation of cementum will be ascertained using tissue separation and recombination techniques. A correlated ultrastructural study will describe the morphological events associated with cellular differentiation. These data will provide valuable information as to the mechanisms involved in root formation.