Mechanochemical control of epidermal stem cell divisions by B-plexins
Open Access
- 26 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-17
- https://doi.org/10.1038/s41467-021-21513-9
Abstract
The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.Funding Information
- China Scholarship Council (201908080171)
- Deutsche Forschungsgemeinschaft (73111208 - SFB 829, GRK2213)
This publication has 94 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway componentsProceedings of the National Academy of Sciences of the United States of America, 2011
- Yap1 Acts Downstream of α-Catenin to Control Epidermal ProliferationCell, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientationNature, 2011
- The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivoProceedings of the National Academy of Sciences of the United States of America, 2011
- Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skinProceedings of the National Academy of Sciences of the United States of America, 2011
- Plexin B1 Suppresses c-Met in Melanoma: A Role for Plexin B1 as a Tumor-Suppressor Protein through Regulation of c-MetJournal of Investigative Dermatology, 2010
- Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cellsOncogene, 2009
- Semaphorin 4D/Plexin-B1–mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activityThe Journal of cell biology, 2006