Epithelial junctions maintain tissue architecture by directing planar spindle orientation

Nature. 2013 Aug 15;500(7462):359-62. doi: 10.1038/nature12335. Epub 2013 Jul 21.

Abstract

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. Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer, 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 delamination 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Drosophila / cytology*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Intercellular Junctions / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • Actins
  • Drosophila Proteins