CP 27 GENE FUNCTION IN TOOTH DEVELOPMENT

说明(改编自调查员摘要)：本提案 重点介绍了新基因cp27在形态发生和分子水平上的功能。 牙齿发育过程中发出的信号。最近克隆了CP27 来自胚胎11期小鼠文库，并在 申请人的实验室(Diekwich等人1999年)。CP27高度展示 牙齿发育中两个不同定位的限制性表达模式 发育：(1)牙板上皮-间充质交界处 (2)帽状期牙齿器官的星状网状结构。 首席调查员的初步数据表明，CP27是一种 发育中牙齿器官的细胞外基质蛋白和一个关键的 正常牙齿形态发生中的分子因素。目前的建议是 设计(I)确定CP27在形态发生中的功能和 在牙齿发育初期的信号传递，以及(Ii)确定 星状网中CP27与细胞外基质的关系 综合。该项目的长期目标是了解监管机构 通过组织特异性分析CP27在牙齿形态发生中的作用 基因表达的机制。提出了四个具体目标来解决 CP27是发育中的细胞外基质分子的假说 牙齿器官对牙齿形态发生的启动和 对于牙冠形成的形态发生控制。具体目标1提出 确定CP27在大鼠脑内的时空表达和定位 发育中的牙齿器官。特定目标2建议进行研究，以表征 CP27调控细胞增殖和生长的机制 牙齿发育。具体目标3将确定CP27对 牙齿发育中的细胞凋亡、失巢和细胞命运。具体目标4提出 CP27对细胞形态和组织调控作用的研究 发育中的牙齿器官的结构。拟议的研究将确定 CP27在上皮-间充质相互作用中的作用 在牙齿发育过程中。了解CP27的功能可能会为 为开发治疗颅面疾病的新型临床辅助器具奠定了基础。

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.