CP 27 GENE FUNCTION IN TOOTH DEVELOPMENT

CP 27 基因在牙齿发育中的功能

• 批准号: 6489659
• 负责人: Tom Diekwisch
• 金额: $ 27.28万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489659
• 关键词: BCL2 gene /protein; actins; antisense nucleic acid; apoptosis; cartilage development; cell cell interaction; cell growth regulation; cysteine endopeptidases; dental development; developmental genetics; embryo /fetus tissue /cell culture; enzyme activity; epithelium; extracellular matrix proteins; fibroblast growth factor; gene expression; gene targeting; genetically modified animals; integrins; laboratory mouse; mesenchyme; organ culture; p53 gene /protein; recombinant proteins; tooth

DESCRIPTION (Adapted from the Investigator's Abstract): The present proposal focuses on the function of a novel gene cp27 in the morphogenesis and molecular signaling that occurs during tooth development. CP27 has been recently cloned from an embryonic stage 11 mouse library and completely sequenced in the applicant's laboratory (Diekwisch et al. 1999). CP27 demonstrates highly restricted expression patterns in two distinct localizations during tooth development: (i) at the epithelial- mesenchymal interface of dental lamina stage tooth germs and (ii) in the stellate reticulum of cap stage tooth organs. The Principal Investigator's preliminary data suggest that CP27 is an extracellular matrix protein of the developing tooth organ and a critical molecular factor in normal tooth morphogenesis. The present proposal is designed (i) to determine the function of CP27 in the morphogenesis and signaling during initial tooth development, and (ii) to establish the role of CP27 in the stellate reticulum in relationship to extracellular matrix synthesis. The long-term goals of this project are to understand the regulatory role of CP27 during tooth morphogenesis through analysis of the tissue specific mechanisms of gene expression. Four specific aims are proposed to address the hypothesis that CP27 is an extracellular matrix molecule in the developing tooth organ that is critical both to the initiation of tooth morphogenesis and to the morphogenetic control of tooth crown formation. Specific Aim 1 proposes to determine the temporospatial expression and localization of CP27 in the developing tooth organ. Specific Aim 2 proposes studies to characterize the mechanism of CP27 regulating cellular proliferation and growth at the onset of tooth development. Specific Aim 3 will determine the effect of CP27 on apoptosis, anoikis, and cell fate in tooth development. Specific aim 4 proposes studies to evaluate the role of CP27 controlling cell shape and tissue architecture of the developing tooth organ. The proposed studies will determine the function of CP27 in the epithelia1-mesenchymal interactions that occur during tooth development. Understanding the function of CP27 may provide the basis for the development of novel clinical aids for craniofacial diseases.

描述（根据调查员的摘要改编）：本提案 着重于新型基因CP27在形态发生和分子中的功能 发育过程中发生的信号传导。 CP27最近被克隆了 从胚胎阶段11鼠标库，完全在 申请人的实验室（Diekwisch等，1999）。 CP27表现高度 牙齿中两个不同局部的限制表达模式 开发：（i）在牙齿层的上皮 - 间质界面 齿轮牙齿器官的星状网状器官中的牙齿细菌和（ii）。 主要研究者的初步数据表明CP27是 发育中的牙科器官的细胞外基质蛋白和关键 正常牙齿形态发生中的分子因子。目前的建议是 设计（i）来确定CP27在形态发生和 在初始牙齿发育过程中发出信号，（ii）确定 与细胞外基质关系的星状网状中的CP27 合成。该项目的长期目标是了解监管 通过分析组织特异性CP27在牙齿形态发生过程中的作用 基因表达的机制。提出了四个具体目标来解决 假设CP27是发育中的细胞外基质分子 对牙齿形态发生和 对牙冠形成的形态发生控制。特定目标1提出 确定CP27在 发展牙科器官。具体目标2提出了研究以表征 CP27调节细胞增殖和生长时的机制 牙齿发育。特定的目标3将确定CP27对 牙齿发育中的细胞凋亡，Anoikis和细胞命运。特定目标4提出 评估CP27控制细胞形状和组织的作用的研究 发育中的牙科器官的建筑。拟议的研究将确定 CP27在发生的上皮相互作用中的功能 在牙齿发育期间。了解CP27的功能可能会提供 开发新型颅面疾病临床辅助工具的基础。