Temporal inactivation of epithelial Isl1 in adult mice leads to incisor enamel defects

成年小鼠上皮 Isl1 的暂时失活导致门牙釉质缺陷

基本信息

批准号：
9444153
负责人：
Andrew H. Jheon
金额：
$ 15.98万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9444153
关键词：
Adult Ameloblasts Amelogenesis Amelogenesis Imperfecta Biological Assay Candidate Disease Gene Cells Cervical ChIP-seq DNA Binding DNA Sequence Data Defect Dental Dental Enamel Dental caries Dental crowns Dentistry Development Diagnostic Ectopic Expression Enamel Formation Enhancers Epithelial Epithelium Foundations Future Gene Expression Gene Targeting Generations Genes Genetic Genetic Transcription Hardness High-Throughput Nucleotide Sequencing Human Human body In Situ Hybridization Incisor Inherited Intervention Studies Investigation Light Maintenance Methods Molecular Mus Natural regeneration Oral cavity Organ Pathway interactions Plant Roots Predisposition Preventive Process Proteins RNA Regulation Research Role Signal Pathway Solid Stem cells Techniques Therapeutic Thick Tissues Tooth Crowns Tooth Loss Tooth eruption Tooth root structure Tooth structure Wild Type Mouse adult stem cell ameloblastin amelogenin analog chromatin immunoprecipitation differential expression experimental study human tissue in vivo innovation interest islet malformation mineralization mouse model notch protein novel precursor cell public health relevance response transcription factor transcriptome sequencing

项目摘要

Project Summary/Abstract Enamel is the outer covering of teeth and is unique in that it is the hardest tissue in our body and one of the few human tissues that cannot regenerate. This inability for human enamel to regenerate is attributed to the loss of ameloblasts or enamel-forming cells and their precursor cells upon eruption of teeth into the oral cavity. Thus, it would be powerful if we could direct adult stem cells that normally do not generate enamel to make ameloblasts and unravel the molecular mechanisms involved. I have generated a mouse model that can be induced to produce ectopic ameloblasts from non-enamel forming, adult stem cells with spatial- and temporal- specific inactivation of a gene called Islet1 (Isl1). The identification of ISL1 target genes and genetic networks will reveal new pathways for investigation into numerous questions regarding enamel formation or amelogenesis. A comprehensive molecular understanding of amelogenesis is important for potential future innovations and improvements to current diagnostic, preventive, and therapeutic methods in dentistry.

项目摘要/摘要搪瓷是牙齿的外覆盖，是独一无二的，因为它是我们体内最难的组织很少无法再生的人体组织。人类搪瓷无法再生的这种无法归因于牙齿爆发进入口腔后，叶片细胞或牙釉质形成细胞及其前体细胞的丧失。因此，如果我们可以指导通常不会产生搪瓷的成年干细胞，那将是强大的成熟细胞并揭示所涉及的分子机制。我已经生成了一个可以是的鼠标模型诱导的是由非仿形的成年干细胞带有空间和时间 - 一个称为ISLET1（ISL1）的基因的特异性失活。 ISL1靶基因和遗传网络的鉴定将揭示新的调查途径，以了解有关搪瓷形成或醒目。对未来的潜在未来重要的分子理解对未来很重要牙科中当前诊断，预防和治疗方法的创新和改进。