NOTCH SIGNALING AND VERTEBRATE LIMB DEVELOPMENT

NOTCH信号传导和脊椎动物肢体发育

基本信息

项目摘要

DESCRIPTION (adapted from investigator's abstract): During vertebrate embryogenesis patterning signals emanate from very discrete centers like the Hensen's node, the midbrain-hindbrain junction or, in the case of the limb, the zone of polarizing activity (ZPA) of the apical ectodermal ridge (AER). It has become evident that many of the molecules that control developmental pathways in insects have homologous counterparts in vertebrates. The AER is required for vertebrate limb outgrowth. Formation of the ridge relies on the previous establishment of the dorso-ventral limb axis. The investigator has cloned a gene, r-fng, which is expressed in the dorsal ectoderm and in the ridge. Ectopic expression experiments indicate that r-fng is able to induce additional AERs suggesting that the AER develops from tissue that is expressing high levels of r-fng adjacent to tissue that is not, i.e. a r-fng boundary. A similar mechanism has been proposed in Drosophila, where the fng gene plays a pivotal role in wing development. Identification of the existence of a common signaling process that mediates the formation of the Drosophila wing margin and the vertebrate AER will be quite surprising, even in light of previously demonstrated homologies between the two phylogenetic groups, and it will require the isolation of downstream molecules. In Drosophila, activation of fng induces a cascade of events that results in the activation of the expression of Serrate, Notch, Vestigial, Cut and Wingless at the dorso-ventral boundary. The investigator has cloned chick homologues of Serrate, Notch and Cut and shown they are expressed in the AER. By using wild type and limb mutant embryos, the investigator will study the consequences of disrupting Notch signaling for establishing and positioning the vertebrate AER. The molecules described above are also required during embryogenesis for other processes like neurogenesis and somitogenesis. This suggests that during limb development, somitogenesis, or neurogenesis, a similar combination of genetic building blocks could be used again and again. Understanding the way these genetic bricks interact with each other in order to position and establish the AER will prove to be a rewarding enterprise, not only from the point of view of limb development, but also from a more general perspective of unraveling how evolution has utilized the same combination of molecules to establish other signaling centers during vertebrate development.
描述(改编自研究者摘要):在脊椎动物 胚胎发生模式信号从非常离散的中心发出, 亨森氏结,中脑-后脑交界处,或者,在肢体的情况下, 顶端外胚层嵴(AER)的极化活动区(ZPA)。 很明显,许多控制发育的分子 昆虫中的途径在脊椎动物中具有同源对应物。 AER是 是脊椎动物四肢生长所必需的 山脊的形成依赖于 之前建立的背腹肢轴。 研究者 克隆了一个基因,r-fng,它在背外胚层和 岭 异位表达实验表明r-fng能够 诱导额外的AER,表明AER是从 表达高水平的R-FNG的邻近组织,即R-FNG 边界 在果蝇中也提出了类似的机制, fng基因在翅发育中起着关键作用。 识别 存在一个共同的信号传导过程,介导的形成, 果蝇翅缘和脊椎动物的AER会相当惊人,即使 根据先前证明的两个系统发育之间的同源性, 基团,它将需要下游分子的隔离。 在 在果蝇中,fng的激活诱导了一系列事件, Serrate、Notch、Vestigial、Cut和 在背腹交界处无翅。 调查员克隆了奇克 Serrate,Notch和Cut的同源物,并显示它们在 AER。 通过使用野生型和肢体突变胚胎,研究人员将 研究中断Notch信号传导的后果, 定位脊椎动物AER。 上述分子也是 在胚胎发育过程中,神经发生和 体节发生 这表明在肢体发育,体节发生, 或神经发生,类似的遗传构建块组合可能是 一次又一次地使用。 了解这些基因砖相互作用的方式 彼此之间,为了定位和建立AER将被证明是 这是一项有益的事业,不仅从肢体发育的角度来看, 也是从一个更普遍的角度来解释进化是如何 利用相同的分子组合来建立其他信号传导, 在脊椎动物的发育过程中。

项目成果

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Juan Carlos Izpisua Belmonte其他文献

Juan Carlos Izpisua Belmonte的其他文献

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{{ truncateString('Juan Carlos Izpisua Belmonte', 18)}}的其他基金

Generation of functional organs and tissues using organism interspecific blastocyst complementation
利用生物体种间囊胚互补生成功能器官和组织
  • 批准号:
    9360608
  • 财政年份:
    2016
  • 资助金额:
    $ 35.51万
  • 项目类别:
Generation of functional organs and tissues using organism interspecific blastocyst complementation
利用生物体种间囊胚互补生成功能器官和组织
  • 批准号:
    10182224
  • 财政年份:
    2016
  • 资助金额:
    $ 35.51万
  • 项目类别:
Generation of functional organs and tissues using organism interspecific blastocyst complementation
利用生物体种间囊胚互补生成功能器官和组织
  • 批准号:
    8949083
  • 财政年份:
    2016
  • 资助金额:
    $ 35.51万
  • 项目类别:
Improving cell fate conversion by tracking cells and RNA over time and space
通过随时间和空间追踪细胞和 RNA 来改善细胞命运转换
  • 批准号:
    9249928
  • 财政年份:
    2015
  • 资助金额:
    $ 35.51万
  • 项目类别:
Improving cell fate conversion by tracking cells and RNA over time and space
通过随时间和空间追踪细胞和 RNA 来改善细胞命运转换
  • 批准号:
    9063144
  • 财政年份:
    2015
  • 资助金额:
    $ 35.51万
  • 项目类别:
Reconstruction and Modeling of Networks Involved in Cardiomyocyte Differentiation
心肌细胞分化相关网络的重建和建模
  • 批准号:
    7667986
  • 财政年份:
    2007
  • 资助金额:
    $ 35.51万
  • 项目类别:
Reconstruction and Modeling of Networks Involved in Cardiomyocyte Differentiation
心肌细胞分化相关网络的重建和建模
  • 批准号:
    7477213
  • 财政年份:
    2007
  • 资助金额:
    $ 35.51万
  • 项目类别:
Reconstruction and Modeling of Networks Involved in Cardiomyocyte Differentiation
心肌细胞分化相关网络的重建和建模
  • 批准号:
    7292828
  • 财政年份:
    2007
  • 资助金额:
    $ 35.51万
  • 项目类别:
Interaction of BMP, WNT and SHH in the Vertebrate Limb
脊椎动物肢体中 BMP、WNT 和 SHH 的相互作用
  • 批准号:
    6734200
  • 财政年份:
    2002
  • 资助金额:
    $ 35.51万
  • 项目类别:
Interaction of BMP, WNT and SHH in the Vertebrate Limb
脊椎动物肢体中 BMP、WNT 和 SHH 的相互作用
  • 批准号:
    6623427
  • 财政年份:
    2002
  • 资助金额:
    $ 35.51万
  • 项目类别:

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一种通过鸡蛋机械诱导血管将功能化性腺结构连接到鸡胚胎的方法
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