Molecular Mechanisms in Development

发育中的分子机制

基本信息

项目摘要

Project Summary/Abstract The goal of this program is to understand how informational molecules that pattern tissues and embryos distribute in space and time during development. We study signaling in Drosophila, investigating the Decapentaplegic, Hedgehog, FGF, EGF, Wg, Notch-Delta and Bicoid morphogen signaling proteins. Our thesis is that the mechanisms that move these proteins from their sources and distribute them to their targets involve cellular machines and organelles whose actions precisely regulate protein movement. Our work has identified novel processes that mediate movement of morphogen signaling proteins in tissues and embryos, and this proposal describes the approaches we will take to further characterize these processes and the machines and organelles that drive them. This work has its origins in two separate investigations. The first began with an analysis of the roles and functions of the engrailed (en) segmentation gene. Like most vertebrates, the Drosophila embryo undergoes a mid-blastula transition (MBT) prior to gastrulation, but the early stages of Drosophila development have unusual features - 13 synchronous, rapid nuclear divisions without cytokinesis. Although the dogma has been that the zygotic genome does not contribute to pre-MBT development, we discovered that zygotic gene expression in nuclear cycle 2 embryos is essential for normal development. We discovered functionally important zygotic en expression in nuclear cycle 2 embryos and identified a small cohort of genes expressed by the pre-blastoderm embryo. We also discovered that the Bicoid concentration gradient that organizes the embryo A/P axis forms from protein that is made in stage 14 oocytes and functions prior to nuclear cycle 7. These findings are the basis for the proposed program that investigates patterning in the early embryo and that already reveals that our understanding of this early, critical stage of development must change radically. The second began with our discovery of cytonemes, specialized filopodia that are involved in cell-cell signaling. This discovery led us to propose that signaling proteins move between cells in a manner similar to the way neurotransmitters exchange between pre- and post-synaptic cells – by transferring between signaling cells at synapses. Our work has established that synapses are present in the Drosophila wing imaginal disc at sites of cytoneme contact, that they involve proteins that have previously been shown to function and to be required at neuronal synapses, and that they are essential for paracrine signaling between non-neuronal cells. We have also obtained strong experimental evidence that cytonemes ferry signaling proteins between producing and receiving cells and we have identified several unexpected properties of cytonemes that have significant implications for mechanisms of pathfinding and signal transduction. The work we pursue develops new tools for imaging cytonemes and builds upon our previous findings to determine the roles, composition and functions of these remarkable organelles and this fascinating mechanism of contact-based signaling.
项目总结/摘要 这个项目的目标是了解组织和胚胎的信息分子是如何 在空间和时间上的分布。我们研究果蝇的信号, Decapentaplegic、Hedgehog、FGF、EGF、Wg、Notch-Delta和Bicoid形态原信号传导蛋白。我们 我的论点是,将这些蛋白质从它们的来源转移到它们的目标的机制, 涉及细胞机器和细胞器,其作用精确地调节蛋白质运动。我们的工作 鉴定了介导组织和胚胎中形态发生素信号蛋白运动的新过程, 这一建议描述了我们将采取的进一步表征这些过程的方法, 驱动它们的机器和细胞器。 这项工作有它的起源在两个独立的调查。第一部分首先分析了这些角色, enrailed(en)分割基因的功能。像大多数脊椎动物一样,果蝇的胚胎经历了一个 中期囊胚过渡(MBT)在原肠胚形成之前,但果蝇发育的早期阶段, 不寻常的特点- 13同步,快速核分裂没有胞质分裂。虽然教条已经 合子基因组对前MBT的发育没有贡献,我们发现合子基因 在核周期2胚胎中的表达对于正常发育是必需的。我们发现功能 在核周期2胚胎中重要的合子en表达,并确定了一小群表达的基因 由前胚盘胚胎发育而成。我们还发现,组织细胞的Bicoid浓度梯度 胚胎A/P轴由14期卵母细胞中产生的蛋白质形成,并在核周期7之前起作用。 这些发现是研究早期胚胎模式的计划的基础, 已经揭示了我们对这个早期的,关键的发展阶段的理解必须彻底改变。 第二个始于我们发现细胞丝,这是一种参与细胞间信号传递的专门丝状伪足。 这一发现使我们提出,信号蛋白在细胞之间的移动方式类似于 神经递质在突触前和突触后细胞之间交换-通过在信号细胞之间转移, 突触我们的工作已经证实,突触存在于果蝇翅的成虫盘中, 细胞丝接触,它们涉及的蛋白质,以前已被证明是功能和所需的, 神经元突触,并且它们对于非神经元细胞之间的旁分泌信号传导是必需的。我们有 我还获得了强有力的实验证据,细胞丝之间的渡轮信号蛋白的生产和 接收细胞,我们已经确定了几个意想不到的性质的细胞素,具有显着的 对寻路和信号转导机制的影响。我们所从事的工作是开发新的工具 并建立在我们以前的研究结果,以确定角色,组成和功能 这些非凡的细胞器和这种迷人的基于接触的信号机制。

项目成果

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THOMAS B. KORNBERG其他文献

THOMAS B. KORNBERG的其他文献

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{{ truncateString('THOMAS B. KORNBERG', 18)}}的其他基金

Molecular mechanisms in development
发展中的分子机制
  • 批准号:
    10406603
  • 财政年份:
    2017
  • 资助金额:
    $ 24.74万
  • 项目类别:
Molecular Mechanisms in Development
发育中的分子机制
  • 批准号:
    9894651
  • 财政年份:
    2017
  • 资助金额:
    $ 24.74万
  • 项目类别:
Molecular mechanisms in development
发展中的分子机制
  • 批准号:
    10621277
  • 财政年份:
    2017
  • 资助金额:
    $ 24.74万
  • 项目类别:
Tumor cytonemes, a new target for tumor suppression
肿瘤细胞因子,肿瘤抑制的新靶点
  • 批准号:
    9247168
  • 财政年份:
    2016
  • 资助金额:
    $ 24.74万
  • 项目类别:
Hedgehog signaling and signal transduction
Hedgehog信号传导和信号转导
  • 批准号:
    8632014
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:
Hedgehog signaling and signal transduction
Hedgehog信号传导和信号转导
  • 批准号:
    9193088
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:
Gene regulation and function in early embryos
早期胚胎的基因调控和功能
  • 批准号:
    8840979
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:
Hedgehog signaling and signal transduction
Hedgehog信号传导和信号转导
  • 批准号:
    8987583
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:
Gene regulation and function in early embryos
早期胚胎的基因调控和功能
  • 批准号:
    8630961
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:
Gene regulation and function in early embryos
早期胚胎的基因调控和功能
  • 批准号:
    8998035
  • 财政年份:
    2014
  • 资助金额:
    $ 24.74万
  • 项目类别:

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谷盗胚层母体蛋白梯度的建立及其功能
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囊胚胚胎中果蝇转录组的多重原位可视化
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Analysis of Blastoderm-Specific Genes in Drosophila
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    8710451
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    1987
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BLASTODERM - SPECIFIC GENE EXPRESSION IN DROSOPHILA
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  • 批准号:
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    1986
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BLASTODERM - SPECIFIC GENE EXPRESSION IN DROSOPHILA
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Analysis of Blastoderm-Specific Genes in Drosophila
果蝇胚盘特异性基因分析
  • 批准号:
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    1984
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Developmental Genetics of Blastoderm Formation: Pupal LethalWith a Maternal Effect
胚盘形成的发育遗传学:蛹致死与母体效应
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    1971
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