Development of the leopard gecko as a model to study in vivo tooth replacement

开发豹纹壁虎作为研究体内牙齿替换的模型

• 批准号: 9387334
• 负责人: JOY M. RICHMAN
• 金额: $ 10.54万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387334
• 关键词: Adult; Agonist; Alligators; Ameloblasts; Anesthesia procedures; Animal Model; Animals; Biomedical Engineering; Biomedical Research; Bite; Black Panther; Cells; Childhood; Data; Defect; Dental; Dentists; Dentition; Deposition; Development; Drug Delivery Systems; Embryo; Employee Strikes; Environment; Epithelial Cells; Epithelium; Evolution; Excision; Fishes; Fossils; Future; Gene Expression; Gene Expression Profiling; General Anesthesia; Generations; Genes; Goals; Grant; Homeostasis; Human; Human Genetics; Iguanas; Implant; Jaw; Label; Learning; Life; Lizards; Longitudinal Studies; Mammals; Mesenchymal Stem Cells; Methods; Minerals; Modeling; Modernization; Molecular; Monitor; Movement; Mucous Membrane; Mus; Natural regeneration; Odontoblasts; Odontogenesis; Operative Surgical Procedures; Pathway interactions; Pattern; Periodontium; Pharmaceutical Preparations; Phenotype; Postdoctoral Fellow; Process; Reptiles; Research; Rock Wallabies; Role; Shark; Side; Signal Pathway; Signal Transduction; Site; Snakes; Source; Speed; Stem cells; Syndrome; Testing; Time; Tissues; Tooth eruption; Tooth regeneration; Tooth structure; Unerupted Tooth; WNT Signaling Pathway; Waxes; Work; bone; craniofacial; deciduous tooth; dental surgery; experimental study; gain of function; healing; in vivo; innovation; insight; juvenile animal; mature animal; mouse model; novel; permanent tooth; transcriptome; transcriptome sequencing

7. PROJECT SUMMARY The long-term goal of the proposed research is gain fundamental insights into the process of tooth replacement. We hope to learn how the dentition is patterned across the jaw and to identify some of the key molecules and cells required to kick-start tooth replacement in adult tissues. In the future, our work will form the basis for bioengineering of tooth replacements. The project is specifically aimed at studying tooth replacement in a non-traditional animal model, the leopard gecko because this animal, unlike mouse, can replace its teeth throughout life. The rationale for choosing this particular lizard is as follows: 1) reptiles and mammals are amniotes and thus share a common ancestor. Therefore discoveries are more likely to be applicable to human than those on fish or the derived mouse dentition, 2) adult geckos have large numbers of teeth that are replaced throughout life, 3) gecko teeth are only attached to bone on the labial side, leaving the lingual successional lamina accessible to experimental manipulation, 4) the tooth replacement cycle is much shorter than other reptiles such as alligators and iguanas so phenotypes will be visible sooner, 5) leopard geckos are readily available from pet suppliers and animals are easy to handle. 6) we have already studied this animal extensively and have characterized the shedding and eruption of teeth over time. The gecko offers unique access to the developing adult dentition compared to mouse, fish and shark models. Specifically, we have developed ways to serially record the whole dentition while the animals are still alive including taking miniature wax bites and photographing fluorescent teeth that were labelled with a special compound taken up by mineralizing tissues. The ability to monitor the effects of dental surgery to the dental lamina in living animals is not possible in other models. We will use this grant to optimize surgery and drug delivery systems to study the adult gecko dentition in 4D. The aims are: 1) to use surgery to disrupt the dental lamina and partially formed dentition in order to isolate the key cells required for tooth initiation. 2) To manipulate the WNT signaling pathway during in vivo tooth replacement and then to study the effect on patterning of the dentition, proliferation and downstream gene expression changes. Innovative methods of animal anesthesia will permit precision surgical procedures to be carried out such as bead implants. The synergistic research environment consists of the PI who is a pediatric dentist and two post-doctoral fellows with backgrounds in dental development and evolution.

7.项目摘要 这项研究的长期目标是获得对牙齿发育过程的基本认识， 更换.我们希望了解牙齿是如何在颌骨上形成图案的， 启动成人组织中牙齿替换所需的分子和细胞。在未来，我们的工作将形成 牙齿替换生物工程的基础。该项目是专门针对研究牙齿 在非传统的动物模型中，豹壁虎是替代品，因为这种动物与小鼠不同， 一生都要更换牙齿。选择这种特殊蜥蜴的理由如下：1）爬行动物和 哺乳动物都是灵长类动物，因此有着共同的祖先。因此，发现更有可能是 适用于人类的比鱼类或衍生的小鼠齿系，2）成年壁虎有大量的 壁虎的牙齿在一生中都会更换，3）壁虎的牙齿只附着在唇侧的骨头上， 舌侧继承板易于实验操作; 4）牙替换周期长 比鳄鱼和鬣蜥等其他爬行动物短，所以表型会更快被发现，豹 壁虎可从宠物供应商处容易地获得，并且动物易于处理。6)我们已经研究过了 动物广泛，并具有随着时间的推移牙齿脱落和萌出的特征。壁虎提供 与小鼠、鱼类和鲨鱼模型相比，它具有独特的进入发育中的成年牙列的途径。我们特别 已经开发出了在动物还活着的时候连续记录整个牙列的方法， 微型蜡咬和拍摄荧光牙齿，这些牙齿被贴上一种特殊的化合物， 通过矿化组织。监测牙科手术对活体动物牙板影响的能力 这在其他型号中是不可能的。我们将利用这笔赠款来优化手术和药物输送系统，以研究 成年壁虎的牙列目的是：1）使用手术破坏牙板， 形成的齿列，以分离出牙齿形成所需的关键细胞。2)操纵WNT 在体内牙齿替换过程中的信号通路，然后研究对牙列图案化的影响， 增殖和下游基因表达变化。创新的动物麻醉方法将允许 精确的外科手术，如珠植入。协同研究环境 由一名儿科牙医PI和两名具有牙科背景的博士后研究员组成 发展和演变。