The overall goal of this proposal is to identify regulatory genes that are involved in the initial inductive events of odontogenesis using the differential display method. Our previous investigations indicate that mandibular epithelium prior to day E12 has odontogenic potential and can organize a dental papillae in NC-derived mesenchymal tissues of the mouse hyoid arch. These results indicate that hyoid mesenchyme has odontogenic potential which is expressed upon interactions with inductive signals from odontogenic epithelium and also suggest that there are genes regulating odontogenesis that are expressed in the mouse mandibular epithelium and but not expressed in the mouse hyoid arch epithelium. Experiments in specific aim #1 of this proposal are designed to identify the odontogenic regulatory genes that are differentially expressed in mandibular and hyoid epithelium. In addition, the current literature raises the possibility that a combination of two growth factors EGF and BMP-4 may be involved in the inductive events in odontogenesis. While the effects of EGF may be predominately in the epithelium, BMP-4, may influence the transcription of a number of genes in the dental mesenchyme. Experiments in the specific aim #2 are designed to examine the causal regulatory roles of each growth factor and the combination of the growth factors roles in the initiation phase of odontogenesis by examining the effects of a) antisense oligomers to these growth factors genes, and b) growth factor agarose-releasing beads on the cascade of events characteristic of the initiation phase of odontogenesis.