Role of Cilia in Mammalian Tooth Patterning

纤毛在哺乳动物牙齿图案中的作用

基本信息

批准号：
7934454
负责人：
Courtney Jeanne Haycraft
金额：
$ 11.06万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-18 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934454
关键词：
Alleles Ameloblasts Bardet-Biedl Syndrome Cells Cilia Cilium Microtubule Complex Data Defect Dental Enamel Dental Pulp Dentin Dentition Development Disease Ectoderm Ectoderm Cell Elements Embryo Embryonic Development Epithelium Exhibits Failure Fibroblast Growth Factor Generations Genes Genetic Goals Histology Homeostasis Human Hypodontia In Situ Hybridization Incisor Lead Left Limb structure Link Liquid substance Mammalian Cell Mesenchymal Mesenchyme Molecular Molecular Genetics Morphogenesis Mus Mutant Strains Mice Mutation Neural Tube Closure Odontoblasts Organelles Pathology Patients Pattern Physical condensation Plant Roots Polydactyly Positioning Attribute Pregnancy Primary Dentition Process Proteins Pulp Chambers Randomized Regulation Role Signal Pathway Signal Transduction Signal Transduction Pathway Staging Staining method Stains Structure Syndrome Tamoxifen Techniques Testing Tissues Tooth structure Transgenic Organisms Work base bone cell motility cell type kinetosome molecular marker mutant oral cavity epithelium oral ectoderm permanent tooth postnatal promoter public health relevance recombinase response smoothened signaling pathway teeth diastema tool

项目摘要

DESCRIPTION (provided by applicant): Cilia are microtubule-based organelles that have long been observed on most mammalian cells. While their presence has been known, their diverse functions in mammalian development and signaling are poorly understood. Cilia have recently been shown to be essential for hedgehog signaling, PDGFRAA signaling and in modulating Wnt responses. Tooth development in mice is initiated during embryogenesis and requires complex signaling between the oral ectoderm and underlying mesenchyme. As development progresses, ectodermal cells contribute to the superficial structures of the tooth including the enamel while the mesenchyme differentiates into many cell types including the dental pulp cells and odontoblasts which secrete dentin below the enamel. Cilia have been identified on the odontoblasts and mice with partial loss of cilia function have defects in the patterning of the teeth suggesting a role for cilia during the patterning and development of the murine dentition. The goal of this application is to investigate cilia function in tooth formation using a conditional allele of the cilia gene Tg737 and an inducible Cre recombinase to disrupt cilia at two distinct stages of tooth development. The role of cilia during tooth initiation and morphogenesis will be investigated by examining the patterning and development of teeth. After cilia disruption, the resulting teeth will be examined using histology and in situ hybridization. Overall the data obtained will provide preliminary to support more detailed studies. PUBLIC HEALTH RELEVANCE: A growing number of pleiotropic syndromes have been associated with mutations in proteins localized to the cilium and/or basal body and defects in tooth number or structure are evident in patients. In order to better understand how cilia/basal body defects lead to alterations in the dentition, additional work is necessary.

描述（由申请人提供）：纤毛是基于微管的细胞器，在大多数哺乳动物细胞上长期观察到。尽管他们的存在已知，但它们在哺乳动物发育和信号传导中的多样功能知之甚少。最近已证明纤毛对于刺猬信号，PDGFRAA信号传导和调节WNT响应至关重要。小鼠的牙齿发育是在胚胎发生过程中启动的，需要在口腔外胚层和基础间质之间进行复杂的信号传导。随着发育的进展，外胚层细胞有助于牙齿的浅表结构，包括牙釉质，而间充质分化为许多细胞类型，包括牙齿浆细胞和牙糖细胞，这些细胞分泌牙釉质下方的牙本质。在纤毛功能的部分丧失的小鼠上已经鉴定出纤毛在牙齿的模式中存在缺陷，这表明在鼠牙列的图案和发育过程中，纤毛的作用。该应用的目的是使用纤毛基因TG737的条件等位基因研究纤毛的功能，并在牙齿发育的两个不同阶段中破坏纤毛。纤毛在牙齿启动和形态发生中的作用将通过检查牙齿的图案和发育来研究。纤毛干扰后，将使用组织学和原位杂交检查所得的牙齿。总体而言，所获得的数据将提供初步以支持更详细的研究。公共卫生相关性：越来越多的多效性综合征与患者的纤毛和/或基底体的蛋白质中的突变有关，并且患者的牙齿数或结构缺陷很明显。为了更好地理解纤毛/基础身体缺陷如何导致牙列发生变化，需要进行其他工作。