The Role of Wnt Signaling in Early Tooth Development

Wnt 信号在早期牙齿发育中的作用

基本信息

批准号：
8909597
负责人：
Rebecca Kim
金额：
$ 3.84万
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：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8909597
关键词：
Ablation Address Adult Affect Alleles Anterior Apoptosis Biological Biology Biomedical Engineering Blood Vessels Bone Resorption Cell Proliferation Cells Cheek structure Complete Denture Data Dental Dental Implants Dental crowns Dentistry Dentures Development Developmental Biology Embryo Embryonic Development Epithelial Epithelium Failure Future Gene Targeting Goals Homeostasis Image Immunohistochemistry In Situ Hybridization In Situ Nick-End Labeling Inferior Label Lead Life Mandible Measures Mechanics Mediating Mesenchymal Mesenchyme Molecular Morphology Mus Mutant Strains Mice Mutation Natural regeneration Odontogenesis Oral Oral cavity Organ Organogenesis Osseointegration Partial Denture Pathway interactions Pattern Phenotype Physical condensation Plant Roots Play Population Positioning Attribute Preparation Regenerative Medicine Reporter Role Shapes Side Signal Pathway Signal Transduction Site Staging Staining method Stains Stem cells Tamoxifen Testing Therapeutic Tissue Engineering Tissues Tooth structure Transgenic Organisms Up-Regulation base beta catenin gain of function improved insight loss of function migration mineralization mouse model progenitor public health relevance recombinase regenerative response restorative dentistry

项目摘要

DESCRIPTION (provided by applicant): The Wnt signaling pathway plays a central role in embryonic development and adult tissue homeostasis. Wnt signaling can be categorized into canonical and non-canonical, depending on which effectors relay signals in Wnt-responsive cells. The canonical Wnt signaling pathway is mediated by ß-catenin, whereas non-canonical pathways are ß-catenin-independent. An important unsolved question in developmental biology is how canonical Wnt signaling regulates early stages of tooth development (odontogenesis). One of the major limitations in uncovering the role of Wnt signaling in tooth development has been a lack of specific markers for dental progenitor cells. Previous studies utilized general activation and ablation of Wnt signaling in oral epithelial and mesenchymal tissues to study how it regulates odontogenesis. However, this broad targeting complicates our understanding of the relationship between Wnt signaling and odontogenesis. We have recently discovered that transient expression of Fgf8 at E11.5 marks dental epithelial progenitor cells (DEPCs). Building on this finding, I activated Wnt signaling specifically in DEPCs, and in contrast to the normally occurring invagination of the epithelium into the underlying dental mesenchyme, I found that the epithelium evaginated into the oral cavity. This observation led me to hypothesize that canonical Wnt signaling regulates the position of DEPCs along the superior-inferior axis. Through this project, I will further explore the role of canonical Wnt signaling during tooth development by assessing the Wnt- responsiveness of DEPCs, and by taking gain- and loss-of-function approaches to evaluate the regulatory role of Wnt signaling in tooth development from the molecular to the organ level. Understanding the mechanism underlying invagination of dental epithelium, as well as the relationship between the migration pattern of DEPCs and the resulting dental morphology, is crucial for understanding the mechanics of tooth development. Thus, this study can provide significant insight into basic tooth biology as well as for regenerative medicine, such as therapeutic dental tissue engineering.

描述（通过应用程序）：Wnt信号通路在胚胎发育中起着核心作用，而成人组织稳态可以分为规范和规范信号通路。 Wnt信号的牙齿发育的早期阶段（牙本质发生）了解Wnt信号传导与牙胎之间的关系。牙齿间充质的基础。牙齿上皮的机制，牙齿形态产生的机制对于牙齿发育的力学至关重要。