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首页> 外文学位 >Insights into intracellular events of the planar cell polarity pathway: A new paradigm for the mechanisms of dishevelleds and dishevelled dependent effector proteins.
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Insights into intracellular events of the planar cell polarity pathway: A new paradigm for the mechanisms of dishevelleds and dishevelled dependent effector proteins.

机译：洞悉平面细胞极性途径的细胞内事件：衣衫and和衣衫dependent依赖的效应蛋白机制的新范式。

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摘要

Dishevelled (Dvl) proteins are key transducers of Wnt signaling and are encoded by members of a multi-gene family in vertebrates. We report here divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression in the mouse. Moreover, we find that the expression patterns of Dvl genes in the chick diverge significantly from those of Xenopus. In addition, in hemichordates, one of the outgroups to chordates, we find that the one Dvl gene is dynamically expressed in a tissue-specific manner. Using knockdowns, we find that Dvl1 and Dvl2 are required for early neural crest specification and for somite segmentation. Most strikingly, we report a novel role for Dvl3 in the maintenance of differentiated muscle and the development of the Xenopus sclerotome. Together, these data demonstrate that that the expression patterns and developmental functions of specific Dvl genes have diverged significantly during chordate evolution.;The planar cell polarity (PCP) signaling pathway is essential for embryonic development because it governs diverse cellular behaviors, and the "core PCP" proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the "PCP effector" proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signaling, but they have never been investigated in a mammal and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice display neural tube defects, polydactyly, and skeletal dysmorphologies that stem from defective ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we establish a central role for Fuz in membrane trafficking, showing that Fuz is essential for apical trafficking of ciliogenesis factors in ciliated cells and also for exocytosis in secretory cells. We identify a novel, Rab-related small GTPase as an interaction partner for Fuz, and this GTPase also is essential for ciliogenesis and secretion. These results are significant because they provide novel insights into the mechanisms by which developmental regulatory systems like PCP signaling interface with fundamental cellular systems such as the vesicle trafficking machinery.
机译：杂散蛋白（Dvl）是Wnt信号转导的关键转导子，由脊椎动物的多基因家族成员编码。我们在这里报告非洲爪蟾胚胎中所有三个Dvl基因的不同组织特异性表达模式，这与它们在小鼠中的表达形成了鲜明的对比。此外，我们发现小鸡中Dvl基因的表达模式与非洲爪蟾有显着差异。此外，在半hor酸盐中，除草索之外，我们发现一个Dvl基因以组织特异性方式动态表达。使用击倒，我们发现Dvl1和Dvl2是早期神经c规范和体节分割所必需的。最引人注目的是，我们报道了Dvl3在维持分化的肌肉和非洲爪蟾硬核刀的发展中的新作用。总之，这些数据表明，特定的Dvl基因的表达模式和发育功能在脊索动物进化过程中发生了显着差异。平面细胞极性（PCP）信号通路对于胚胎发育至关重要，因为它控制着多种细胞行为，并且“核心PCP“蛋白，例如Disheveled和Frizzled，已得到广泛表征。相比之下，“ PCP效应子”蛋白（例如Intu和Fuz）仍未得到充分研究。这些蛋白质对于PCP信号转导至关重要，但从未在哺乳动物中进行过研究，其细胞生物学活性仍然完全未知。我们在这里报告Fuz突变小鼠显示神经管缺陷，多指和骨骼畸形的起源于有缺陷的睫毛发生。使用生物信息学和体内粘膜纤毛上皮的成像，我们建立了Fuz在膜运输中的核心作用，表明Fuz对于纤毛细胞中纤毛生成因子的顶端运输以及分泌细胞的胞吐作用至关重要。我们确定了一种新颖的，与Rab相关的小GTP酶作为Fuz的相互作用伴侣，并且该GTPase对纤毛发生和分泌也至关重要。这些结果之所以有意义，是因为它们为诸如P​​CP信号等发展性调控系统与基本细胞系统（如囊泡运输机器）对接的机制提供了新颖的见解。

著录项

  • 作者

    Gray, Ryan Scott.;

  • 作者单位

    The University of Texas at Austin.;

  • 授予单位 The University of Texas at Austin.;
  • 学科 Biology Cell.;Biology Bioinformatics.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 153 p.
  • 总页数 153
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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