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Epithelial junctions maintain tissue architecture by directing planar spindle orientation

机译：上皮连接通过指导平面纺锤体定向来维持组织结构

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摘要

During epithelial cell proliferation, planar alignment of the mitotic spindle coordinates the local process of symmetric cell cleavage with the global maintenance of polarized tissue architecture~(1,2). Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer~(3-6), the in vivo mechanisms regulating mitotic spindle orientation remain elusive. Here we demonstrate that the actomyosin cortex and the junction- localized neoplastic tumour suppressors Scribbled and Discs large 1 have essential roles in planar spindle alignment and thus the control of epithelial integrity in the Drosophila imaginal disc. We show that defective alignment of the mitotic spindle correlates with cell dela-mination and apoptotic death, and that blocking the death of misaligned cells is sufficient to drive the formation of basally localized tumour-like masses. These findings indicate a key role for junction- mediated spindle alignment in the maintenance of epithelial integrity, and also reveal a previously unknown cell-death- mediated tumour-suppressor function inherent in the polarized architecture of epithelia.
机译：在上皮细胞增殖过程中，有丝分裂纺锤体的平面排列协调了对称细胞分裂的局部过程与极化组织结构的整体维持（1,2）。尽管提出了破坏平面纺锤体排列以引起上皮向间质转化和癌变的研究（3-6），但调节有丝分裂纺锤体定向的体内机制仍然难以捉摸。在这里，我们证明了放线菌素皮层和交界处的局部肿瘤抑癌剂Scribbled和Discs large 1在平面纺锤体对齐中具有重要作用，从而在果蝇假想盘中控制上皮完整性。我们表明，有丝分裂纺锤体的有缺陷的对齐方式与细胞分层和凋亡死亡相关，并且阻止错位细胞的死亡足以驱动基础定位的肿瘤样肿块的形成。这些发现表明连接介导的纺锤体对齐在维持上皮完整性中的关键作用，并且还揭示了极化的上皮结构固有的先前未知的细胞死亡介导的肿瘤抑制功能。

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  • 来源
    《Nature》 |2013年第7462期|359-362|共4页
  • 作者

    Yu-ichiro Nakajima; Emily J. Meyer; Amanda Kroesen; Sean A. McKinney; Matthew C. Gibson;

  • 作者单位

    Stowers Institute for Medical Research ,1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Stowers Institute for Medical Research ,1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Stowers Institute for Medical Research ,1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Stowers Institute for Medical Research ,1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Stowers Institute for Medical Research ,1000 East 50th Street, Kansas City, Missouri 64110, USA,Department of Anatomy and Cell Biology, University of Kansas Medical Center,3901 Rainbow Boulevard,Kansas City, Kansas 66160, 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);
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  • 正文语种 eng
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