TISSUE INTERACTIONS IN PALATAL SHELF CLOSURE
TISSUE INTERACTIONS IN PALATAL SHELF CLOSURE
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
关键词:
SDS polyacrylamide gel electrophoresis basement membrane collagen embryo /fetus cell /tissue enzyme activity extracellular matrix proteins fibronectins histogenesis hyaluronate image processing immunocytochemistry in situ hybridization laboratory mouse laminin mesenchyme metalloendopeptidases organ culture palate plasminogen activator plasminogen activator inhibitors polymerase chain reaction protein degradation radioimmunoassay syndecan tissue inhibitor of metalloproteinases
中文摘要
这项研究的长期目标是了解细胞和
决定正常次级腭形态发生的分子因素。
构成腭的细胞外基质(ECM)分子
间质基质和基底膜对该过程很重要。
腭间质 ECM 排列为支架,由
主要由纤连蛋白 (Fn)、胶原蛋白 III(Col ]III) 和
透明质酸 (Ha),在预期体内提前一天发挥作用
腭架重新定向。 如果架子被移植到器官培养中
此时,它们会重新定位并显示 ECM 的伴随变化
分布。 IV 型胶原蛋白 (Col IV) 和分布的变化
上皮基底膜局部区域的层粘连蛋白(Ln)和
Syndecan(Sn) 在间充质中的分布立即发生变化
这些区域下方也伴随着架子的改造。 显然,
一旦这些 ECM 结构建立起来,腭架就
能够重塑以实现重新定位。 试点数据表明
必要的改变可能涉及金属蛋白酶(MMP)和
纤溶酶原激活剂(PA)。 现有的工作还表明,特别是
在发育过程中,ECM、MMP、PA 及其激活剂之间的相互作用
抑制剂决定了 ECM 的特性。 然而,迄今为止还没有
关于这些酶在次级味觉中的作用的工作已经完成
形态发生。 根据目前的知识,有以下假设
提出:Ha介导的货架扩张导致重新定位
是由临时组织结构的改变引导的
Fn 和 Col III 分布的空间局部变化
间隙基质和 Col III 和 IV、Ln 和 Sn 在特定局部
覆盖上皮的基底膜区域和
间质紧邻其下方。 这些变化涉及
蛋白酶介导的 ECM 分子降解。 三具体
提出的目标是检验这一假设: (1) 描述
腭架 ECM 支架的时空发展
从上颌突到腭架出现的时间
结构具有功能性; (2) 识别 MMP、PA 及其
腭架中存在的抑制剂
体内和体外形态发生并确定其时间序列
外观和空间分布; (3) 确定效果
抑制或激活上颚基质降解蛋白酶
形态发生以及间质的组成和组织
ECM 结构和基底膜。 器官培养,SDS-PAGE,
酶谱分析、RNA 表型分析、原位杂交和
结合图像处理和分析进行免疫组织化学分析
形态测量学将用于实现这些目标。 结果
这些研究将增加我们对 ECM 和
上颚形态发生过程中的基质降解酶。 这样一个
理解可能会导致更准确地识别可以
破坏该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.
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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
The distribution of syndecan during murine secondary palate morphogenesis.
小鼠次级腭形态发生过程中多配体的分布。
DOI:
--
发表时间:
1992
期刊:
Journal of craniofacial genetics and developmental biology
影响因子:
--
作者:
[Brinkley,L, Morris-Wiman,J, Bernfield,M]
通讯作者:
Bernfield,M
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批准号:3218252
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项目类别:
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依托单位:
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项目类别:
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项目类别:
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依托单位:
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批准号:3509658
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负责人:JOYCE A MORRIS-WIMAN
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依托单位:
TISSUE INTERACTIONS IN PALATAL SHELF CLOSURE
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批准号:2128876
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项目类别:
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资助金额:$16.11万
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财政年份:1989
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依托单位:
海外基金