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首页> 外文学位 >Dact1 functions in the planar cell polarity pathway during vertebrate gastrulation.
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Dact1 functions in the planar cell polarity pathway during vertebrate gastrulation.

机译：Dact1在脊椎动物气化过程中在平面细胞极性途径中发挥作用。

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摘要

The Dact family (also known as Dapper/Frodo) of cytoplasmic scaffold proteins are expressed during embryonic development and have been shown to modulate developmentally important signaling pathways such as the Wnt pathway. To gain a better understanding of the developmental stages and tissues in which Dacts function, the embryonic expression pattern of the mouse Dact family was characterized. Dact1 is expressed in mesoderm derived tissue (i.e. presomitic mesoderm and somites) and in the primitive streak, where gastrulation occurs. To determine if Dact1 is required for gastrulation, mouse mutants in the Dact1 gene were analyzed during gastrulation stages (e7.0-e8.5). These data indicate that at the 6 somite stage, Dact1 mutants have posterior morphological defects in the region of the primitive streak reminiscent of phenotypes associated with abnormalities in convergent extension movements necessary to elongate the embryo. These posterior defects are associated with disruptions in downstream readouts of the Planar Cell Polarity Pathway and not the Wnt/beta-catenin pathway. The morphological differences seen in Dact1 mutants arise due to the abnormal upregulation of membrane Vangl2 and E-cadherin protein levels in primitive streak cells undergoing epithelial-mesenchymal transition (EMT) preceeding cell migration. Vangl2 Loop-tail mutants show the opposite effect with a reduction in Vangl2 membrane localization in these cells. Importantly, crossing these two mutations (i.e. making Dact1 mutants also heterozygous for the Vangl2 Loop-tail mutation) restored Vangl2 membrane levels at the primitive streak and rescued Dact1 embryological phenotypes. These data identify a role for Dact1 in regulating appropriate levels of the Planar Cell Polarity protein Vangl2 necessary for EMT and cell migration during mouse gastrulation.
机译：细胞质支架蛋白的Dact家族（也称为Dapper / Frodo）在胚胎发育过程中表达，并已被证明可调控重要的信号通路，如Wnt通路。为了更好地了解Dacts的发育阶段和组织，我们对小鼠Dact家族的胚胎表达模式进行了表征。 Dact1在中胚层来源的组织（即早体中胚层和体节）中以及在发生胃形成的原始条纹中表达。为了确定是否需要Dact1进行胃泌乳，在胃泌乳阶段（e7.0-e8.5）对Dact1基因的小鼠突变体进行了分析。这些数据表明在6个somite阶段，Dact1突变体在原始条纹区域具有后部形态缺陷，使人联想到与延长胚胎所需的会聚延伸运动异常相关的表型。这些后部缺陷与平面细胞极性途径而不是Wnt /β-catenin途径的下游读数中断有关。在Dact1突变体中看到的形态学差异是由于在细胞迁移之前经历上皮-间质转化（EMT）的原始条纹细胞中膜Vangl2和E-钙粘蛋白蛋白水平的异常上调引起的。 Vangl2 Loop-tail突变体显示出相反的效果，减少了这些细胞中Vangl2膜的定位。重要的是，越过这两个突变（即使Dact1突变体对于Vangl2 Loop-tail突变也是杂合的）可以恢复原始条纹的Vangl2膜水平，并拯救了Dact1胚胎表型。这些数据确定了Dact1在调节小鼠胃胚形成过程中EMT和细胞迁移所必需的平面细胞极性蛋白Vangl2的适当水平中的作用。

著录项

  • 作者

    Suriben, Rowena Mae Obina.;

  • 作者单位

    University of California, San Francisco.;

  • 授予单位 University of California, San Francisco.;
  • 学科 Biology Cell.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 124 p.
  • 总页数 124
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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