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首页> 外文期刊>Nature >Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries.
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Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries.

机译：Notch信号限制了发育中的斑马鱼动脉中的血管生成细胞行为。

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摘要

Recent evidence indicates that growing blood-vessel sprouts consist of endothelial cells with distinct cell fates and behaviours; however, it is not clear what signals determine these sprout cell characteristics. Here we show that Notch signalling is necessary to restrict angiogenic cell behaviour to tip cells in developing segmental arteries in the zebrafish embryo. In the absence of the Notch signalling component Rbpsuh (recombining binding protein suppressor of hairless) we observed excessive sprouting of segmental arteries, whereas Notch activation suppresses angiogenesis. Through mosaic analysis we find that cells lacking Rbpsuh preferentially localize to the terminal position in developing sprouts. In contrast, cells in which Notch signalling has been activated are excluded from the tip-cell position. In vivo time-lapse analysis reveals that endothelial tip cells undergo a stereotypical pattern of proliferation and migration during sprouting. In the absence of Notch, nearly all sprouting endothelial cells exhibit tip-cell behaviour, leading to excessive numbers of cells within segmental arteries. Furthermore, we find that flt4 (fms-related tyrosine kinase 4, also called vegfr3) is expressed in segmental artery tip cells and becomes ectopically expressed throughout the sprout in the absence of Notch. Loss of flt4 can partially restore normal endothelial cell number in Rbpsuh-deficient segmental arteries. Finally, loss of the Notch ligand dll4 (delta-like 4) also leads to an increased number of endothelial cells within segmental arteries. Together, these studies indicate that proper specification of cell identity, position and behaviour in a developing blood-vessel sprout is required for normal angiogenesis, and implicate the Notch signalling pathway in this process.
机译：最近的证据表明，不断增长的血管新芽由具有不同细胞命运和行为的内皮细胞组成。但是，尚不清楚什么信号决定这些芽细胞的特性。在这里，我们显示，Notch信号对于将血管生成细胞的行为限制到斑马鱼胚胎中发育的节段动脉中的尖端细胞是必要的。在没有Notch信号成分Rbpsuh（无毛重组结合蛋白抑制剂）的情况下，我们观察到节段动脉过度发芽，而Notch激活则抑制了血管生成。通过镶嵌分析，我们发现缺少Rbpsuh的细胞优先定位在正在发育的新芽中的末端位置。相反，已经激活Notch信号传导的细胞从末端细胞位置中排除。体内时移分析显示，内皮尖细胞在发芽过程中经历了增殖和迁移的定型模式。在没有Notch的情况下，几乎所有发芽的内皮细胞都表现出尖细胞行为，导致节段动脉内细胞数量过多。此外，我们发现flt4（与fms相关的酪氨酸激酶4，也称为vegfr3）在节段动脉尖端细胞中表达，并在缺刻缺席的情况下在整个新芽中异位表达。 flt4的丢失可以部分恢复Rbpsuh缺乏节段动脉中正常的内皮细胞数量。最后，Notch配体dll4（δ样4）的丢失也导致节段动脉内内皮细胞数量增加。总之，这些研究表明，正常血管生成需要在发育中的血管新芽中正确识别细胞身份，位置和行为，并暗示该过程中的Notch信号通路。

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  • 来源
    《Nature》 |2007年第7129期|P.781-784|共4页
  • 作者

    SiekmannAF; LawsonND;

  • 作者单位

    Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 364 Plantation Street, Worcester, Massachusetts 01605, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

    Cells; Endothelial cell; Zebrafish; angiogenesis; 细胞; 斑马鱼;

    机译：Cells;Endothelial cell;Zebrafish;angiogenesis;细胞;斑马鱼;

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