CEMENTOGENESIS: ROLE OF HERTWIG'S EPITHELIAL ROOT SHEATH

牙骨质形成：HERTWIG 上皮根鞘的作用

• 批准号: 6772438
• 负责人: Margarita Zeichner-David
• 金额: $ 31.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772438
• 关键词: apoptosis; cell cell interaction; cell line; cell migration; cell proliferation; cementum; dental development; dental structure; gene targeting; genetically modified animals; genotype; histogenesis; homologous transplantation; in situ hybridization; laboratory mouse; mesenchyme; microarray technology; odontoblasts; organ culture; protein biosynthesis; terminal nick end labeling; tooth enamel; tooth root; transcription factor

DESCRIPTION (provided by applicant): Despite the tremendous knowledge related to the growth and transcription factors that regulate tooth development, there is still a lack of information related to the factors involved at later stages of tooth development, when the mineralized tissues are formed, and an even greater paucity of information as to the factors that regulate root development. It is the long-term objective of this study to understand the process of root development at the morphologic, cellular and molecular levels including the mechanisms underlying root dentin and cementum formation as well as root attachment to periodontal ligament in the healthy periodontium. In this application, we will focus on the role of Hertwig's Epithelial Root Sheath (HERS) cells in root development. Although the role of HERS cells in root formation is widely accepted, the precise function and fate of these cells remains controversial. Functions suggested for these cells have ranged from a pure structural entity (subdivide the dental ectomesenchymal tissues into dental papilla and dental follicle), to regulators of the timing of root development, to inducers for mesenchymal cells differentiation into cementoblasts, to being cementoblast cells precursors. In this competing renewal we will test the hypothesis that that root development is initiated by HERS cells through dynamic and reciprocal interactions with the surrounding mesenchyme resulting in budding morphogenesis and there is a unique gene associated with these tissues that is regulated by the NFI-C transcription factor. We propose to test this hypothesis by taking advantage of a newly created Nfi-c (Nuclear Factor I-C) knockout mice knock whose unique phenotype is that it lacks the formation of roots. In addition we will use established immortal cell lines (HERS, Dental Papillae Mesenchyme (DPM), dental follicle) to accomplish the following Specific Aims: To determine the initial events leading to root morphogenesis; To determine what kind of cell interactions are necessary for root development; To determine the molecules associated with root development; To determine the role of the molecules identified in root development. The use of a wide range of technology including in situ hybridization, tissue recombination, organ culture, cell culture, microarrays technology, etc. will provide the data required to accomplish our specific alms. The data generated in this study will provide much needed information related to root development, the role of HERS in this process and the regulatory factors involved in root formation. Although rare, individuals with root agenesis have been documented.

描述（由申请人提供）：尽管与调节牙齿发育的生长和转录因子相关的知识有很大的知识，但仍缺乏与牙齿发育后期涉及的因素，形成矿化组织的涉及的因素有关的信息，并且与调节根源发育的因素相关的信息较少。这项研究的长期目标是了解形态，细胞和分子水平的根部发育过程，包括根牙和骨质形成的机制以及健康牙周牙周韧带的根附着。在此应用中，我们将重点关注赫特维格的上皮根鞘（HERS）在根发育中的作用。尽管HERS细胞在根部形成中的作用被广泛接受，但这些细胞的精确功能和命运仍然存在争议。这些细胞所建议的功能范围从纯结构实体（将牙齿外层组织细分为牙皮乳头和牙齿卵泡）到根发育时间的调节剂到诱导间充质细胞的诱导剂，以分化为胶质细胞的细胞，再到是胶质细胞细胞的前体。在这种竞争的更新中，我们将测试以下假设：该假设是HERS细胞通过与周围间充质的动态和相互相互作用而引发的，从而导致形态发生萌芽，并且存在与NFI-C转录因子调节的独特基因。我们建议通过利用新创建的NFI-C（核因子I-C）敲除小鼠敲除，其独特的表型是它缺乏根的形成。此外，我们将使用已建立的不朽细胞系（HERS，牙皮乳头间充质（DPM），牙卵泡）来实现以下特定目的：确定导致根部形态发生的初始事件；确定根源开发需要哪种类型的细胞相互作用；确定与根发育相关的分子；确定鉴定在根发育中的分子的作用。使用广泛的技术，包括原位杂交，组织重组，器官培养，细胞培养，微阵列技术等，将提供完成我们特定施舍所需的数据。这项研究中产生的数据将提供与根发展，此过程中的作用以及涉及根部形成的监管因素有关的急需信息。尽管很少见，但已记录了具有根源的人。