Epithelial junctions maintain tissue architecture by directing planar spindle orientation

The Drosophila tumour suppressors Scribbled and Discs large 1 are found to be essential regulators of planar spindle alignment during epithelial cell division; aberrant effects of spindle alignment are shown to be corrected through apoptosis, and the suppression of this mechanism can result in epithelial dysplasia and tumorigenesis. Discs large, Scribbled involved in spindle alignment Mitotic spindle formation is a key step towards the segregation of chromosomes into two daughter cells during mitosis, and the precise alignment of mitotic spindles to the plane of the epithelium is thought to be important in maintaining tissue integrity. The in vivo determinants of planar spindle orientation remain unknown. Here Matthew Gibson and colleagues demonstrate that the actomyosin cortex and junction-localized tumour suppressors Scribbled and Discs large 1 are essential regulators of planar spindle alignment. Defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and furthermore, blocking death of misaligned cells is sufficient to drive the formation of tumour-like cell masses. The authors propose that the deleterious effects of aberrant spindle alignment are corrected by apoptosis and that suppression of this mechanism could result in epithelial dysplasia and tumorigenesis. 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.sup.1,2. Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer.sup.3,4,5,6, 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 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.
Author(s): Yu-ichiro Nakajima [sup.1] , Emily J. Meyer [sup.1] , Amanda Kroesen [sup.1] , Sean A. McKinney [sup.1] , Matthew C. Gibson [sup.1] [sup.2] Author Affiliations: (1) Stowers Institute for [...]