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MOLECULAR BASIS OF DEVELOPMENTAL CELL INTERACTIONS

MOLECULAR BASIS OF DEVELOPMENTAL CELL INTERACTIONS
发育细胞相互作用的分子基础
批准号:
6182400
负责人:
J LAWRENCE MARSH
金额:
$28.16万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-06-01 至 2001-05-31

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中文摘要
翻译
尽管在操纵分泌物的基因方面取得了巨大的进步 信号分子,分泌型造影剂的作用与接触依赖 驱动图案化和极性信号的相互作用 目前尚不清楚具体途径。此外,很少有好的候选分子 可能介导假定的接触依赖的信号传导已被描述。 这些是理解图案形成的关键问题,它们解决了 “发育中的细胞”这一观察的机制基础 通过组织增长和变化来应对位置的变化 根据所导出的位置信息来判断发展命运 并通过与邻居的互动进行解释“(Wolpert,1969)。 细胞内起作用的基因克隆,如蓬乱的和蓬乱的 而下游的无翼等分泌分子可以异位组织 以特定位置的方式形成图案。在最简单的解释中, 这些观察表明,局部细胞的相互作用驱动了图案化 当克隆被诱导的时候。然而,刺激监管增长的克隆 也可以导致分泌分子的异位激活,如无翼 或者是十足瘫痪。我们进一步发现,工作组发出的信号抑制了 民进党和签证的表达。因此,要解决隐秘的作用 形态致病与接触相关的相互作用,必须分开 分泌型分子对接触介导型分子的影响 互动。在这里,我们建议进行实验,以实现这一点。这个 Dsh和sgg克隆的组织模式的潜力 单元格或相邻单元格无法生成或响应 将确定可能的形态致病原DPP和WG;因此,分离出 接触依赖机制的影响与扩散机制的影响 信号。这种克隆人刺激生长的潜力独立于 命运规范也将被直接评估。脂肪基因将会是 测试以确定脂肪是否是调解接触的候选者- 依赖于信号。继续研究以阐明其结构基础 DSH在传输基于继电器的极性信号中的作用与 天文台将发出秘密WG信号。Dsh、sgg和dsh丢失的影响 脂肪活性对连接相关亚细胞定位的影响 还将检查蛋白质和细胞亲和力,以测试 组织结构涉及不同位置的假设 特定的细胞亲和力。
英文摘要
Despite dramatic advances in the manipulation of genes for secreted signaling molecules, the role of secreted morphogens vs. contact-dependent interactions in driving both the patterning and polarity signaling pathways remains unclear. Further, very few good candidate molecules that might mediate putative contact-dependent signaling have been described. These are key issues for understanding pattern formation and they address the mechanistic basis of the observation that "cells in a developmental field respond to changes in position by organizing growth and changes in developmental fate according to positional information which is derived and interpreted via interactions with their neighbors" (Wolpert, 1969). Clones of genes such as dishevelled and shaggy that act intracellularly and downstream of secreted molecules such as wingless can organize ectopic pattern in a position specific manner. In the simplest interpretation, these observations suggest that local cell interactions drive patterning when clones are induced. However, clones which stimulate regulatory growth can also lead to ectopic activation of secreted molecules such as wingless or decapentaplegic. We have further found that signaling by wg suppresses expression of dpp and visa versa. Thus, to address the role of secreted morphogens vs. contact-dependent interactions, it is essential to separate the effects of secreted molecules from those of contact-mediated interactions. Here we propose experiments to do exactly that. The potential of dsh and sgg clones to organize pattern when either the clonal cells or neighboring cells are unable to produce or respond to the putative morphogens dpp and wg will be determined; thus, isolating the effects due to contact-dependent mechanisms from those due to diffusible signals. The potential of such clones to stimulate growth independent of fate specification will also be directly assessed. The fat gene will be tested to determine whether fat is a candidate for mediating in contact- dependent signaling. Continuing studies to elucidate the structural basis of DSH's role in transmitting a relay based polarity signal vs the secreted wg signal will be conducted. The effect of loss of dsh, sgg and fat activity on the subcellular localization of junction associated proteins and on cell affinities will also be examined to test the hypothesis that tissue organization involves differential position specific cell affinity.
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Role of chromatin remodeling in Huntington's disease
  • 批准号:
    8232854
  • 项目类别:
  • 资助金额:
    $2.78万
  • 财政年份:
    2011
  • 负责人:
    J LAWRENCE MARSH
  • 依托单位:
OPTICAL BIOLOGY (SHARED RESOURCE)
  • 批准号:
    7944544
  • 项目类别:
  • 资助金额:
    $5.22万
  • 财政年份:
    2009
  • 负责人:
    J LAWRENCE MARSH
  • 依托单位:
Quantifying Injury Severity to Assess the Risk of Post-Traumatic Osteoarthritis
  • 批准号:
    7920169
  • 项目类别:
  • 资助金额:
    $20.97万
  • 财政年份:
    2009
  • 负责人:
    J LAWRENCE MARSH
  • 依托单位:
Quantifying Injury Severity to Assess the Risk of Post-Traumatic Osteoarthritis
  • 批准号:
    7677866
  • 项目类别:
  • 资助金额:
    $25.29万
  • 财政年份:
    2008
  • 负责人:
    J LAWRENCE MARSH
  • 依托单位:
海外基金