Cellular and molecular control of tooth morphogenesis

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ABSTRACT Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. Additionally, tooth anomalies are common in many craniofacial syndromes, and the easy accessibility of the oral cavity makes teeth an excellent test case for organ replacement. A thorough understanding of the molecular and cellular processes that drive tooth development will be crucial to efforts to build and repair teeth. The initial step in tooth development involves epithelial invagination that, while representative of a fundamental and widespread morphogenetic motif utilized throughout development, also demonstrates important differences among tooth types. We propose to analyze the early, asymmetrical invagination events in the incisor teeth and to contrast these with the symmetrical invagination of the molar teeth. In Specific Aim 1, we will define the cell dynamics (motions and forces) distinguishing incisor vs. molar formation. In Specific Aim 2, we will determine the mechanism by which FGF signaling modulation controls tooth morphogenesis. In Specific Aim 3, we will apply the spatial and directional effects of FGF and Shh signaling to modify tooth shape.