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.
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http://dx.doi.org/10.1038/nature12335 | DOI Listing |
Open Biol
October 2024
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
SLMAP3 is a constituent of the centrosome and is known to assemble with the striatin-interacting phosphatase and kinase (STRIPAK) complex, where it has been reported to repress Hippo signalling. The global knockout of SLMAP3 in mice results in embryonic/perinatal lethality and stunted growth without changes in the phosphorylation status of YAP. Diverse phenotypes present in the SLMAP3 embryos include reduced body axis, small and abnormal organs resembling defects in planar cell polarity (PCP) signalling, while also displaying the notable polycystic kidneys, a known manifestation of ciliopathies.
View Article and Find Full Text PDFJ Clin Med
August 2024
Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy.
Myotonic dystrophy type 1 (DM1) is a rare multisystemic genetic disorder with motor hallmarks of myotonia, muscle weakness and wasting. DM1 patients have an increased risk of falling of multifactorial origin, and proprioceptive and vestibular deficits can contribute to this risk. Abnormalities of muscle spindles in DM1 have been known for years.
View Article and Find Full Text PDFDevelopment
May 2024
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
The planar orientation of cell division (OCD) is important for epithelial morphogenesis and homeostasis. Here, we ask how mechanics and antero-posterior (AP) patterning combine to influence the first divisions after gastrulation in the Drosophila embryonic epithelium. We analyse hundreds of cell divisions and show that stress anisotropy, notably from compressive forces, can reorient division directly in metaphase.
View Article and Find Full Text PDFJ Pathol
June 2024
Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E-cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E-cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early-stage DGC lesions.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
March 2024
Shanghai Engineering Research Center of Hierarchical Nanomaterials, Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
The advancement of highly secure and inexpensive aqueous zinc ion energy storage devices is impeded by issues, including dendrite growth, hydrogen evolution and corrosion of zinc anodes. It is essential to modify the interface of zinc anodes that homogenizes ion flux and facilitates highly reversible zinc planarized deposition and stripping. Herein, by coupling zinc ion coordination with acid-base neutralization under the driving of electrophoresis, manageable mesoscopic phase separation for constructing chitosan frameworks was achieved, thereby fabricating interconnected mesoporous chitosan membranes based heterogeneous quasi-solid-state electrolytes integrated with anodes.
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