Cellular and molecular control of tooth morphogenesis

摘要 牙齿生物工程引起了人们的极大兴趣，因为龋齿和牙齿脱落是一种重要的 健康问题。此外，牙齿异常在许多颅面综合征中很常见，而且容易出现的 口腔的可及性使牙齿成为器官移植的极佳测试案例。一次彻底的 了解驱动牙齿发育的分子和细胞过程将对努力 建造和修复牙齿。牙齿发育的第一步涉及上皮内陷，而 代表了在整个发育过程中使用的一个基本和广泛的形态发生母题，也 展示了不同牙齿类型之间的重要差异。我们建议分析早期的、不对称的 并将其与磨牙的对称性凹陷进行对比。 在具体目标1中，我们将定义区分门牙和磨牙形成的细胞动力学(运动和力)。 在特定的目标2中，我们将确定成纤维细胞生长因子信号调节控制牙齿的机制 形态发生。在具体目标3中，我们将应用成纤维细胞生长因子和Shh信号的空间和方向性效应来 修改齿形。

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.