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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 [...]

Jellyfish have existed on the earth for around 600 million years and have evolved in response to environmental changes. Hydrozoan jellyfish, members of phylum Cnidaria, exist in multiple life stages, including planula larvae, vegetatively-propagating polyps, and sexually-reproducing medusae. Although free-swimming medusae display complex morphology and exhibit increase in body size and regenerative ability, their underlying cellular mechanisms are poorly understood. Here, we investigate the roles of cell proliferation in body-size growth, appendage morphogenesis, and regeneration using Cladonema pacificum as a hydrozoan jellyfish model. By examining the distribution of S phase cells and mitotic cells, we revealed spatially distinct proliferating cell populations in medusae, uniform cell proliferation in the umbrella, and clustered cell proliferation in tentacles. Blocking cell proliferation by hydroxyurea caused inhibition of body size growth and defects in tentacle branching, nematocyte differentiation, and regeneration. Local cell proliferation in tentacle bulbs is observed in medusae of two other hydrozoan species, Cytaeis uchidae and Rathkea octopunctata , indicating that it may be a conserved feature among hydrozoan jellyfish. Altogether, our results suggest that hydrozoan medusae possess actively proliferating cells and provide experimental evidence regarding the role of cell proliferation in body-size control, tentacle morphogenesis, and regeneration., Competing Interests: The authors declare that they have no competing interests.