Patterning the Vertebrate Dentition Through Replacement and Repair

项目概要/摘要 这项研究的主要目标是了解牙齿再生的分子机制 以及脊椎动物的组织更新。我们的研究得益于实验系统的明确整合 （慈鲷鱼，斑马鱼，小鼠）和一种独特的方法将新的生物学从鱼类转化为哺乳动物 再回来在这个竞争性的续约申请中，我们在上一个项目期间概述了三个 在多个脊椎动物牙齿模型中融合无偏和实验方法的特定目的， 鉴定指导天然全牙替换的细胞群和分子信号（慈鲷和 斑马鱼）和小鼠切牙组织更新。我们要填补的空白是巨大的。五分之一的人类 出现影响牙列的遗传性疾病，几乎100%出现问题（例如蛀牙） 随年龄全世界65岁以上的人中有30%完全没有牙齿。我们的研究将提供 对再生牙齿如何被划分为协调的再生区域这一基本问题的回答 以及哺乳动物牙齿如何从损伤中恢复。洞察力应促进创新 生物启发再生牙科的策略。

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.