CEMENTOGENESIS: ROLE OF HERTWIG'S EPITHELIAL ROOT SHEATH

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非常丰富，但仍然缺乏与牙齿发育后期（矿化组织形成时）所涉及的因子相关的信息，并且更缺乏关于调节牙根发育的因子的信息。本研究的长期目标是从形态、细胞和分子水平了解牙根发育的过程，包括牙根牙本质和牙骨质形成的机制以及健康牙周组织中牙根与牙周膜的附着。在这个应用程序中，我们将集中在赫特维希上皮根鞘（HERS）细胞在根发育中的作用。虽然HERS细胞在根形成中的作用被广泛接受，但这些细胞的确切功能和命运仍然存在争议。这些细胞的功能范围从单纯的结构实体（将牙外胚间充质组织细分为牙乳头和牙囊），到根发育时间的调节剂，到间充质细胞分化为成牙骨质细胞的诱导剂，再到成牙骨质细胞前体。在这种竞争性的更新，我们将测试的假设，即根的发展是由HERS细胞通过动态和相互作用与周围的间充质，导致出芽形态发生，并有一个独特的基因与这些组织，是由NFI-C转录因子调节。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来测试这一假设。此外，我们将使用已建立的永生细胞系（HERS、牙乳头间质（Dental Papillae Mesenchyme，Dental Follicle））来实现以下特定目的：确定导致牙根形态发生的初始事件;确定牙根发育所需的细胞相互作用;确定与牙根发育相关的分子;确定在牙根发育中鉴定的分子的作用。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。在这项研究中产生的数据将提供急需的信息相关的根的发展，HERS在这一过程中的作用和调控因素参与根的形成。虽然罕见，但根发育不全的个体已被记录在案。

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.