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Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Overview of Cell Death01:30

Overview of Cell Death

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Structure of Cadherins01:25

Structure of Cadherins

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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Desmosomes01:05

Desmosomes

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The term desmosome derives from the Greek words "desmo" and "soma" meaning "adhesion bodies." This structure was first observed during the late 1800s and described as small, dense nodules in the epidermis. Desmosomes are button-like structures that help form an interlinked network of intermediate filaments across the cells. These junctions are  essential to hold cells together under mechanical stress and to maintain tissue integrity. Desmosomes are multi-protein...
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Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
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Assessing Signaling Properties of Ectodermal Epithelia During Craniofacial Development
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在外皮性发育不良症中的基因缺陷意味着死亡领域适配器在发育过程中存在.

D J Headon1, S A Emmal, B M Ferguson

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.

Nature
|January 10, 2002
PubMed
概括

研究人员确定了Edaradd,这是一个关键的蛋白质,将Edar受体与信号通路联系起来. 这一发现解释了缺水性外皮皮质质变形症,并突出了发育过程中保存的信号传递.

科学领域:

  • 发展生物学 发展生物学
  • 分子遗传学 分子遗传学
  • 细胞信号传递 细胞信号传递

背景情况:

  • 瘤坏死因子受体 (TNFR) 家庭成员具有死亡域,通过招募适应蛋白来启动信号传递.
  • 埃达是TNFR家族蛋白质,对头发,牙和外皮发育至关重要.
  • 在人类和小鼠中,Edar或其配体Eda的突变会导致低水分外皮发育不良 (HED).

研究的目的:

  • 为了识别与Edar受体相关的死亡域适配蛋白.
  • 为了阐明HED背后的分子机制.
  • 调查死亡受体/适配器在发育过程中的信号保护.

主要方法:

  • 对小鼠纹位置的遗传分析.
  • 蛋白相互作用研究证实了Edaradd与Edar.结合.
  • 在人类骨科医生EDARADD中发现突变.

主要成果:

  • 识别Edaradd (Edar相关死亡域) 作为编码由纹位编码的适应蛋白.
  • 这种纹突变体表现出与埃达尔和埃达突变体相同的HED表型.
  • 埃达拉德与埃达尔的死亡领域相互作用,将其连接到下游的信号通路.

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  • 在一个患有HED的家庭中发现了人类EDARADD的误解突变.
  • 结论:

    • 埃达拉德是埃达尔信号复合体的关键组成部分,对于外皮发育至关重要.
    • 这些发现表明,死亡受体/适配器信号机制在发育和亡过程中都保持不变.
    • 这项研究提供了关键的洞察力,对缺水性外皮皮质变形症的遗传基础.