Mechanochemical control of epidermal stem cell divisions by B-plexins

Chen Jiang, Ahsan Javed, Laura Kaiser, Michele M. Nava, Rui Xu, Dominique T. Brandt, Dandan Zhao, Benjamin Mayer, Javier Fernández-Baldovinos, Luping Zhou, Carsten Höß, Kovilen Sawmynaden, Arkadiusz Oleksy, David Matthews, Lee S. Weinstein, Heidi Hahn, Hermann-Josef Gröne, Peter L. Graumann, Carien M. Niessen, Stefan Offermanns, Sara A. Wickström and Thomas Worzfeld ()
Additional contact information
Chen Jiang: University of Marburg
Ahsan Javed: University of Helsinki
Laura Kaiser: University of Marburg
Michele M. Nava: University of Helsinki
Rui Xu: University of Marburg
Dominique T. Brandt: University of Marburg
Dandan Zhao: University of Marburg
Benjamin Mayer: University of Marburg
Javier Fernández-Baldovinos: University of Marburg
Luping Zhou: University of Marburg
Carsten Höß: University of Marburg
Kovilen Sawmynaden: LifeArc
Arkadiusz Oleksy: LifeArc
David Matthews: LifeArc
Lee S. Weinstein: NIH
Heidi Hahn: University Medical Center Göttingen
Hermann-Josef Gröne: University of Marburg
Peter L. Graumann: University of Marburg
Carien M. Niessen: University of Cologne
Stefan Offermanns: Max-Planck-Institute for Heart and Lung Research
Sara A. Wickström: University of Helsinki
Thomas Worzfeld: University of Marburg

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21513-9

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DOI: 10.1038/s41467-021-21513-9

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