Role of Cilia in Mammalian Tooth Patterning

纤毛在哺乳动物牙齿图案中的作用

• 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
• 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

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，长期以来在大多数哺乳动物细胞中被观察到。虽然它们的存在是已知的，但它们在哺乳动物发育和信号传导中的多种功能却知之甚少。纤毛最近被证明在hedgehog信号传导、PDGFRAA信号传导和调节Wnt反应中是必不可少的。小鼠的牙齿发育始于胚胎发生，需要口腔外胚层和间质之间复杂的信号传导。随着发育的进行，外胚层细胞形成牙齿的表层结构，包括牙釉质，而间充质细胞分化为多种细胞类型，包括牙髓细胞和牙釉质下分泌牙本质的成牙细胞。在成牙细胞中发现了纤毛，部分纤毛功能丧失的小鼠在牙齿形成过程中存在缺陷，这表明纤毛在小鼠牙列的形成和发育过程中起着重要作用。本应用程序的目的是研究纤毛在牙齿形成中的功能，使用纤毛基因Tg737的条件等位基因和可诱导的Cre重组酶在牙齿发育的两个不同阶段破坏纤毛。纤毛在牙齿起始和形态发生中的作用将通过检查牙齿的模式和发育来研究。在纤毛断裂后，将使用组织学和原位杂交检查产生的牙齿。总的来说，获得的数据将为更详细的研究提供初步支持。