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: 7739199
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739199
• 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观察到。虽然它们的存在已为人所知，但它们在哺乳动物发育和信号传导中的不同功能却知之甚少。纤毛最近被证明对于 Hedgehog 信号传导、PDGFRAA 信号传导和调节 Wnt 反应至关重要。小鼠的牙齿发育是在胚胎发生过程中启动的，需要口腔外胚层和底层间充质之间的复杂信号传导。随着发育的进展，外胚层细胞有助于形成包括牙釉质在内的牙齿表面结构，而间充质则分化成许多细胞类型，包括牙髓细胞和在牙釉质下方分泌牙本质的成牙本质细胞。已在成牙本质细胞上发现了纤毛，并且纤毛功能部分丧失的小鼠在牙齿图案中存在缺陷，这表明纤毛在小鼠牙列的图案形成和发育过程中发挥着作用。此应用的目标是使用纤毛基因 Tg737 的条件等位基因和诱导型 Cre 重组酶来研究纤毛在牙齿形成中的功能，以在牙齿发育的两个不同阶段破坏纤毛。通过检查牙齿的模式和发育来研究纤毛在牙齿萌生和形态发生过程中的作用。纤毛破坏后，将使用组织学和原位杂交检查所产生的牙齿。总体而言，获得的数据将为支持更详细的研究提供初步数据。 公共卫生相关性：越来越多的多效性综合征与纤毛和/或基体的蛋白质突变有关，并且患者的牙齿数量或结构缺陷很明显。为了更好地了解纤毛/基体缺陷如何导致牙列改变，需要进行额外的工作。