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- Title
Mechanochemical control of epidermal stem cell divisions by B-plexins.
- Authors
Jiang, Chen; Javed, Ahsan; Kaiser, Laura; Nava, Michele M.; Xu, Rui; Brandt, Dominique T.; Zhao, Dandan; Mayer, Benjamin; Fernández-Baldovinos, Javier; Zhou, Luping; Höß, Carsten; Sawmynaden, Kovilen; Oleksy, Arkadiusz; Matthews, David; Weinstein, Lee S.; Hahn, Heidi; Gröne, Hermann-Josef; Graumann, Peter L.; Niessen, Carien M.; Offermanns, Stefan
- 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. It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.
- Subjects
STEM cells; BASAL cell carcinoma; EPITHELIUM; CELL junctions; CELL proliferation; CELL division
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-21513-9