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 OffermannsSara A. Wickström, Thomas Worzfeld

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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.
Originalspråkengelska
TidskriftNature Communications
ISSN2041-1723
DOI
StatusPublicerad - 26 feb 2021
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi
  • 1184 Genetik, utvecklingsbiologi, fysiologi

Citera det här