The Cichlid Dentition Integrates Tooth Number and Tooth Shape

丽鱼齿列结合了牙齿数量和牙齿形状

基本信息

批准号：
7267992
负责人：
Jeffery Todd Streelman
金额：
$ 17.96万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2009-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Despite a long tradition of study in mammals, important questions remain regarding the genetic and developmental basis of differences in tooth shape. Here, I propose a novel approach to the study of tooth shape. I concentrate on an evolutionary model system that exhibits tremendous diversity in dental patterning. My long-term goal is to identify the genes and the developmental programs that integrate differences in tooth shape and tooth number, within and among species of cichlid fish from Lake Malawi, East Africa. The specific goals of this exploratory research are to (i) fine map a region of the cichlid genome that controls tooth shape and (ii) identify patterns of gene expression that generate correlated differences in cichlid tooth and cusp number. Specific Aim 1. Identify the genetic basis of differences in tooth shape. An approximately 3.5 centimorgan interval on cichlid chromosome 5 explains about 40% of the phenotypic variance in an interspecific cross between cichlid species with bicuspid vs. tricuspid teeth. Using fingerprinted BAG libraries in the closely-related tilapia, I will generate a minimum tiling path across this region and sequence overlapping clones at 30-50x coverage, using new high-throughput DMA sequencing technology. Specific Aim 2. Identify the developmental programs that determine differences in tooth number, tooth spacing and cusp number among cichlid species with divergent dental patterns. I will use in situ hybridization to study the role of a number of candidate loci (Bmp4; Fgf4,8; Pax9; Dlx1,2; Shh; Pitx2; Msx; Barx1; Edar; ectodin) in the generation of novelty in cichlid tooth shape and patterning. Accomplishing the exploratory aims outlined above will provide the foundation required to identify genetic changes involved in tooth shape differences among individuals (Aim 1) and will solve the odontogenic code for species with different dental patterning (Aim 2). Knowledge of the genetic and developmental basis of differences in cichlid tooth patterning will lend general insight into vertebrate odontogenesis and will contribute important comparative data for studies in mouse. Results may identify novel therapeutic targets for human dental disorders that warrant further testing in mammalian models.

描述（由申请人提供）：尽管在哺乳动物中进行了悠久的研究传统，但关于牙齿形状差异的遗传和发育基础仍然存在重要问题。在这里，我提出了一种新的牙齿研究方法。我专注于一种进化模型系统，该系统在牙齿模式中表现出巨大的多样性。我的长期目标是确定来自东非马拉维湖的丽鱼科鱼类和牙齿形状和牙齿数量差异的基因和发展计划。这项探索性研究的具体目标是（i）详细地图丽鱼科基因组的区域，该区域控制牙齿形状，（ii）确定基因表达的模式，这些模式产生了丽鱼科和尖尖数的相关差异。特定目的1。确定牙齿形状差异的遗传基础。丽鱼科染色体上的大约3.5厘米间隔解释了具有双刺与三尖瓣牙齿的酸毛相对于三尖齿的酸性牙间交叉中的40％的表型差异。使用与密切相关的罗非鱼中的指纹袋库，我将使用新的高通量DMA测序技术在30-50x覆盖范围内生成一条最小平铺路径，并在30-50x覆盖范围内重叠克隆。具体目的2。确定确定牙齿牙齿不同牙齿牙齿不同的牙齿数量，牙齿间距和尖数差异的发展程序。我将使用原位杂交来研究许多候选基因座（BMP4; FGF4,8; PAX9; DLX1,2; SHH; pITX2; MSX; MSX; BARX1; EDAR; Ectodin; Ectodin）在Cichlid牙齿形状和策略中的新颖性中。完成上面概述的探索目的将为识别个人之间牙齿形状差异涉及的遗传变化所需的基础（AIM 1），并将解决具有不同牙齿构图的物种的牙源性代码（AIM 2）。了解丽鱼科牙齿模式的遗传和发育基础的知识将对脊椎动物牙肠发生的一般见解，并将为小鼠研究提供重要的比较数据。结果可能会确定需要在哺乳动物模型中进一步测试的人类牙科疾病的新型治疗靶标。