Molecular Dissection of Tooth Shape

描述(由申请人提供)： 牙胚发育是上皮-间充质信号传递的典型例子。与关于牙齿早期发育规范的大量信息相比，人们对导致牙齿形状差异的基因知之甚少。这些信息是理解脊椎动物牙齿多样性背后的机制，哺乳动物异牙的进化，以及某些人类牙齿疾病的根本原因所必需的。在小鼠中没有概括牙齿形状表型的基因敲除，而其他模式生物(斑马鱼、青蛙、雏鸟)要么口腔下巴没有牙齿，要么表现出从根本上衍生的牙列。在这里，描述了一种研究牙齿形态变异的新系统。产于非洲马拉维湖的两种叶斑鱼Labeotroeus fuelleborni(Lf)和Metriaclima Zebra(Mz)分别长有三尖瓣和二尖瓣的牙齿。这项建议描述了来自Lf和Mz杂交的F2鱼的与牙齿形状差异相关的基因组区域的鉴定。通过在同一杂交组合中定位这些基因座，并通过研究候选基因在亲本和杂交胚胎中的表达模式，来评估特定候选基因的作用。这些数据将有助于从分子上理解脊椎动物牙齿形状的差异。

DESCRIPTION (provided by applicant): Odontogenesis is a classic example of epithelial-mesenchymal signaling. In contrast to the bounty of information regarding the specification of early tooth development, little is know about the genes responsible for differences in tooth shape. This information is needed to understand the mechanisms behind vertebrate tooth diversity, the evolution of mammalian heterodonty, and the underlying cause of certain human dental disorders. There are no genetic knock-outs in mouse that recapitulate tooth shape phenotypes and other model organisms (zebrafish, frog, chick) either lack teeth in the oral jaws or exhibit radically derived dentitions. Here, a new system in which to study variance in tooth morphology is described. Labeotropheus fuelleborni (Lf) and Metriaclima zebra (Mz), two species of cichlid fishes from Lake Malawi, Africa have tricuspid and bicuspid teeth respectively. This proposal describes the identification of genomic regions associated with tooth shape differences in F2 fish derived from the inter-cross of Lf and Mz. The role of specific candidate genes is evaluated by mapping these loci in the same cross and by studying patterns of candidate gene expression in parental and hybrid embryos. These data will contribute to a molecular understanding of differences in vertebrate tooth shape.