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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）：尽管对哺乳动物的研究有着悠久的传统，但关于牙齿形状差异的遗传和发育基础的重要问题仍然存在。在这里，我提出了一种研究牙齿形状的新方法。我专注于一个在牙齿图案方面表现出巨大多样性的进化模型系统。我的长期目标是确定东非马拉维湖丽鱼科鱼类内部和物种之间牙齿形状和牙齿数量差异的基因和发育程序。这项探索性研究的具体目标是（i）精细绘制慈鲷基因组中控制牙齿形状的区域，以及（ii）识别在慈鲷牙齿和牙尖数量上产生相关差异的基因表达模式。具体目标 1. 确定牙齿形状差异的遗传基础。慈鲷第 5 号染色体上大约 3.5 厘摩的间隔解释了具有二尖牙和三尖牙的慈鲷物种之间种间杂交中约 40% 的表型差异。在密切相关的罗非鱼中使用指纹 BAG 文库，我将使用新的高通量 DMA 测序技术生成跨该区域的最小平铺路径，并以 30-50 倍覆盖率对重叠克隆进行测序。具体目标 2. 确定决定具有不同牙齿模式的丽鱼科鱼种之间牙齿数量、牙齿间距和牙尖数量差异的发育程序。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；Barx1；Edar；ectodin）在慈鲷牙齿形状和图案的新颖性产生中的作用。实现上述探索性目标将为识别个体之间牙齿形状差异所涉及的遗传变化提供所需的基础（目标1），并将解决具有不同牙齿图案的物种的牙源密码（目标2）。了解慈鲷牙齿图案差异的遗传和发育基础将有助于了解脊椎动物的牙发育，并将为小鼠研究提供重要的比较数据。结果可能会确定人类牙齿疾病的新治疗靶点，并需要在哺乳动物模型中进行进一步测试。