Patterning the Vertebrate Dentition Through Replacement and Repair

项目摘要/摘要 这项研究的主要目标是了解牙齿再生的分子机制。 脊椎动物的组织更新。我们的研究得益于实验系统的显式集成 (Cichlid鱼类、斑马鱼、老鼠)和一种将新生物学从鱼类转换为哺乳动物的独特方法 再回来。在此竞争性续订申请中，我们在前一个项目期的基础上概述了三个 在多个脊椎动物牙齿模型中融合无偏见和实验方法的特定目标 确定引导自然全牙替换的细胞群体和分子信号(慈鱼和 斑马鱼)和小鼠门牙组织更新。我们的目标是填补巨大的空白。五分之一的人类 表现出影响牙列的遗传性疾病，几乎100%出现问题(例如，龋齿) 随着年龄的增长。全世界65岁以上的人中有30%完全没有牙齿。我们提议的研究将提供 关于再生牙如何划分为协调的更新区这一基本问题的答案 和分化，以及哺乳动物牙齿如何从损伤中恢复。洞察力应促进创新 受生物启发的再生牙科的策略。

Project Summary/Abstract The broad goal of the proposed research is to understand molecular mechanisms of tooth regeneration and tissue renewal in vertebrates. Our research benefits from explicit integration of experimental systems (cichlid fishes, zebrafish, mouse) and a unique approach translating new biology from fishes to mammals and back. In this competitive renewal application, we build on the previous project period to outline three Specific Aims that fuse unbiased and experimental approaches in multiple vertebrate tooth models to identify cell populations and molecular signals that direct natural whole-tooth replacement (cichlids and zebrafish) and mouse incisor tissue renewal. The gaps we aim to fill are significant. One in five humans presents with a genetic disorder affecting the dentition and nearly 100% develop problems (e.g, cavities) with age. 30% of people worldwide over the age of 65 lack teeth entirely. Our proposed research will provide answers to the basic question of how regenerating teeth are partitioned into coordinated zones of renewal and differentiation, and how mammalian teeth recover from damage. Insights should promote innovative strategies for bio-inspired regenerative dentistry.