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TISSUE INTERACTIONS IN PALATAL SHELF CLOSURE

TISSUE INTERACTIONS IN PALATAL SHELF CLOSURE
腭架闭合中的组织相互作用
批准号:
2391143
负责人:
JOYCE A MORRIS-WIMAN
金额:
$15.04万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-09-01 至 2001-03-31

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中文摘要
翻译
这项研究的长期目标是了解细胞和 决定正常二次腭部形态发生的分子因素。 构成腭部的细胞外基质(ECM)分子 间质基质和基底膜对这一过程很重要。 腭部间质ECM被安排为支架,由 主要是纤维连接蛋白(FN)、III型胶原(Col)III和 透明质酸(Ha),在体内比预期提前一天起作用 腭架重新定向。如果货架被移植到器官培养中 此时,它们在ECM中重新定位并显示相应的变化 分发。IV型胶原(Col IV)的分布变化及 上皮基底膜局部区域的层粘连蛋白(Ln)和 间充质中Syndecan(锡)分布的即刻变化 这些区域的下部也伴随着陆架改造。显然, 一旦这些细胞外基质结构建立,腭架是 能够重塑以实现重新定向。试点数据表明, 必要的改变可能涉及金属蛋白酶(MMPs)和 纤溶酶原激活剂(PA)。现有的研究还表明,特别是 在发育过程中,ECM、MMPs、PA及其激活剂之间的相互作用 而抑制剂决定了ECM的性质。然而,到目前为止,没有 关于这些酶在次级味觉中的作用的研究已经完成。 形态发生。根据目前的知识,以下假设 提出:Ha介导的导致重新定向的陆架扩张 是由组织结构的改变引导的,这些改变是由时间- FN和Col III在脑内分布的空间局部化变化 间隙基质和特定局域中的Col III和Col IV、Ln和Sn. 覆盖上皮的基底膜面积和 紧随其后的是骨髓间充质。这些变化涉及 蛋白酶介导的细胞外基质分子的降解。三个具体的 提出了检验这一假说的目标:(1)描述 腭架细胞外基质支架材料的时空发育 从上颌突至上颌突出现腭架的时间 结构是功能性的;(2)确定MMP、PA及其 在上颌过程中出现在腭架上的抑制物 体内外形态发生及其时间序列的确定 外观和空间分布的影响;(3)确定 抑制或激活腭部基质降解蛋白 形态发生与间质的组成和组织 细胞外基质结构和基底膜。器官培养,十二烷基硫酸钠-PAGE, 酶谱、RNA表型、原位杂交和 图像处理与分析相结合的免疫组织化学分析 将使用形态测量法来实现这些目标。结果是 这些研究将增加我们对ECM和 腭部形态发生过程中的基质降解酶。这样的一种 了解可能会导致更准确地识别可以 扰乱这一过程,以及那些可能逆转或补偿的过程 破坏性因素或缺陷基因的影响。
英文摘要
The long-term goal of this research is to understand the cellular and molecular factors that determine normal secondary palate morphogenesis. The extracellular matrix(ECM) molecules that compose the palatal interstitial matrix and basement membranes are important to the process. The palatal interstitial ECM is arranged as a scaffolding, composed principally of fibronectin(Fn), collagen III(Col ]III) and hyaluronan(Ha), that is functional by one day before expected in vivo palatal shelf reorientation. If shelves are explanted into organ culture at this time, they reorient and show accompanying changes in ECM distribution. Changes in distribution of collagen IV(Col IV) and laminin(Ln) in local regions of the epithelial basement membrane and changes in syndecan(Sn) distribution in the mesenchyme immediately subjacent to these regions also accompany shelf remodelling. Apparently, once these ECM structures are established, the palatal shelves are capable of remodelling to achieve reorientation. Pilot data suggest the necessary alterations may involve the metalloproteinases(MMPs) and plasminogen activators(PAs). Existing work also suggests, particularly in development, the interplay between ECM, MMPs, PAs and their activators and inhibitors determine the character of an ECM. However, to date no work has been done on the role of these enzymes in secondary palate morphogenesis. In light of current knowledge, the following hypothesis is proposed: The Ha-mediated shelf expansion that leads to reorientation is guided by alterations in tissue architecture resulting from temporo- spatially localized changes in the distribution of Fn and Col III in the interstitial matrix and of Col III and IV, Ln and Sn in specific local areas of the basement membrane of the covering epithelium and the mesenchyme immediately subjacent to it. These changes involve proteinase-mediated degradation of the ECM molecules. Three specific aims are proposed to test this hypothesis: (1) Describe the temporo-spatial development of the palatal shelf ECM scaffolding from the time of emergence of the palatal shelves from the maxillary process until the structure is functional; (2) Identify the MMPs, PAs and their inhibitors that are present in the palatal shelves during palate morphogenesis in vivo and in vitro and determine their temporal sequence of appearance and spatial distribution; (3) Determine the effects of inhibiting or activating the matrix-degrading proteinases on palate morphogenesis and the composition and organization of the interstitial ECM structure and the basement membrane. Organ culture, SDS-PAGE, zymography, RNA phenotyping, in situ hybridization, and immunohistochemistry analyzed by image processing and analysis combined with morphometry will be used to achieve these aims. The results of these studies will increase our knowledge of the interactions of ECM and matrix-degrading enzymes in the process of palate morphogenesis. Such an understanding may lead to more precise identification of agents that can disrupt the process as well as those that might reverse or compensate for the effects of disruptive agents or defective genes.
期刊论文(15)
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会议论文
Changes in mesenchymal cell-basal lamina relationships preceding palatal shelf reorientation in the mouse.
小鼠腭架重新定向之前间充质细胞与基底层关系的变化。
DOI: 10.1002/aja.1001760309
发表时间: 1986
期刊: The American journal of anatomy
影响因子: --
作者: [Brinkley,LL]
通讯作者: Brinkley,LL
The effects of chlorcyclizine-induced alterations of glycosaminoglycans on mouse palatal shelf elevation in vivo and in vitro.
氯环嗪诱导的糖胺聚糖改变对体内和体外小鼠腭架升高的影响。
DOI: --
发表时间: 1982
期刊: Journal of embryology and experimental morphology
影响因子: --
作者: [Brinkley,LL, Vickerman,MM]
通讯作者: Vickerman,MM
Rapid changes in the extracellular matrix accompany in vitro palatal shelf remodelling.
细胞外基质的快速变化伴随着体外腭架重塑。
DOI: 10.1007/bf00191453
发表时间: 1993
期刊: Anatomy and embryology
影响因子: --
作者: [Morris-Wiman,J, Brinkley,L]
通讯作者: Brinkley,L
Occurrence and temporal variation in matrix metalloproteinases and their inhibitors during murine secondary palatal morphogenesis.
小鼠次级腭形态发生过程中基质金属蛋白酶及其抑制剂的出现和时间变化。
DOI: --
发表时间: 1999
期刊: Journal of craniofacial genetics and developmental biology.
影响因子: --
作者: [Morris-Wiman,J, Du,Y, Brinkley,L]
通讯作者: Brinkley,L
10
    Glial Response in a Jaw Muscle Pain Model
    • 批准号:
      7789236
    • 项目类别:
    • 资助金额:
      $21.98万
    • 财政年份:
      2010
    • 负责人:
      JOYCE A MORRIS-WIMAN
    • 依托单位:
    Glial Response in a Jaw Muscle Pain Model
    • 批准号:
      8070507
    • 项目类别:
    • 资助金额:
      $6.25万
    • 财政年份:
      2010
    • 负责人:
      JOYCE A MORRIS-WIMAN
    • 依托单位:
    Glial Response in a Jaw Muscle Pain Model
    Mast Cell Role in Masseter Muscle Repair
    • 批准号:
      6954228
    • 项目类别:
    • 资助金额:
      $18.19万
    • 财政年份:
      2004
    • 负责人:
      JOYCE A MORRIS-WIMAN
    • 依托单位:
    海外基金