CP 27 GENE FUNCTION IN TOOTH DEVELOPMENT

CP 27 基因在牙齿发育中的功能

• 批准号: 6626941
• 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/6626941
• 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（改编自研究者的摘要）：目前的提案 重点关注新基因 cp27 在形态发生和分子生物学中的功能 牙齿发育过程中发生的信号传导。 CP27最近被克隆 来自胚胎 11 期小鼠文库，并在 申请人的实验室（Diekwisch et al. 1999）。 CP27展示了高度 牙齿过程中两个不同定位的限制表达模式 发育：（i）在牙板的上皮-间质界面 阶段牙胚和（ii）在帽阶段牙齿器官的星状网中。 首席研究员的初步数据表明 CP27 是一个 发育中的牙齿器官的细胞外基质蛋白和一个关键的 正常牙齿形态发生的分子因素。目前的建议是 设计 (i) 以确定 CP27 在形态发生中的功能和 初始牙齿发育期间的信号传导，以及（ii）确定 星状网中的 CP27 与细胞外基质的关系 合成。该项目的长期目标是了解监管 通过组织特异性分析 CP27 在牙齿形态发生中的作用 基因表达机制。为解决这一问题，提出了四个具体目标 假设 CP27 是发育中的细胞外基质分子 牙齿器官，对于牙齿形态发生的启动和 牙冠形成的形态发生控制。具体目标 1 提出 确定 CP27 的时空表达和定位 正在发育的牙齿器官。具体目标 2 提出研究来表征 CP27在细胞增殖和生长开始时调节细胞增殖和生长的机制 牙齿发育。具体目标 3 将决定 CP27 对 细胞凋亡、失巢凋亡和牙齿发育中的细胞命运。具体目标4提出 评估 CP27 控制细胞形状和组织作用的研究 发育中的牙齿器官的结构。拟议的研究将确定 CP27 在上皮-间质相互作用中的功能 在牙齿发育过程中。了解 CP27 的功能可以提供 为开发颅面疾病的新型临床辅助工具奠定了基础。