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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development
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Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development

机译:自由曲线参与河马信号传导,是正常斑马鱼前线发育所必需的

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摘要

Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated by the protocadherin Fat in Drosophila. Vertebrates express 4 Fat molecules, Fat1-4. We found that depletion of Fat1 caused cyst formation in the zebrafish pronephros. Knockdown of the PDZ domain containing the adaptor protein Scribble intensified the cyst-promoting phenotype of Fat1 depletion, suggesting that Fat1 and Scribble act in overlapping signaling cascades during zebrafish pronephros development. Supporting the genetic interaction with Fat1, Scribble recognized the PDZ-binding site of Fat1. Depletion of Yes-associated protein 1 (YAP1), a transcriptional co-activator inhibited by Hippo signaling, ameliorated the cyst formation in Fat1 -deficient zebrafish, whereas Scribble inhibited the YAP1-induced cyst formation. Thus, reduced Hippo signaling and subsequent YAP1 disinhibition seem to play a role in the development of pronephric cysts after depletion of Fat1 or Scribble. We hypothesize that Hippo signaling is required for normal pronephros development in zebrafish and that Scribble is a candidate link between Fat and the Hippo signaling cascade in vertebrates.
机译:细胞及其附属物的空间组织受平面细胞极性途径控制,这是由果蝇中的原钙粘蛋白脂肪引发的信号级联。脊椎动物表达4个脂肪分子,即Fat1-4。我们发现Fat1的耗竭导致斑马鱼pronephros中的囊肿形成。包含衔接蛋白Scribble的PDZ结构域的敲低加剧了Fat1耗竭的促进囊肿的表型,表明Fat1和Scribble在斑马鱼前蝶发育期间的重叠信号级联中起作用。支持与Fat1的遗传相互作用,Scribble识别了Fat1的PDZ结合位点。 Yes相关蛋白1(YAP1)的耗竭,一种被河马信号转导抑制的转录共激活因子,改善了Fat1缺陷斑马鱼的囊肿形成,而Scribble抑制了YAP1诱导的囊肿形成。因此,减少的Hippo信号传导和随后的YAP1抑制作用似乎在Fat1或Scribble耗尽后在肾前囊肿的发展中起作用。我们假设在斑马鱼中正常的前ne发育需要Hippo信号传导,并且杂文是Fat与脊椎动物中Hippo信号传导级联之间的候选链接。

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  • 作者单位

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029;

    Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Division of Nephrology, Rheinisch-Westfalische Technische Hochschule Aachen, 52074 Aachen, Germany;

    Leibniz Institute for Age Research-Fritz Lipmann Institute, 07745 Jena, Germany;

    Leibniz Institute for Age Research-Fritz Lipmann Institute, 07745 Jena, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;

    Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany Center for Biological Signaling Studies (bioss), 79104 Freiburg, Germany;

  • 收录信息 美国《科学引文索引》(SCI);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
  • 关键词

    fat; planar cell polarity; polycystic kidney disease;

    机译:脂肪;平面细胞极性多囊肾;

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