Mechanochemical control of epidermal stem cell divisions by B-plexins

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Chen Jiang , Javed , A , Kaiser , L , Nava , M M , Xu , R , Brandt , D T , Zhao , D , Mayer , B , Fernández-Baldovinos , J , Zhou , L , Höß , C , Sawmynaden , K , Oleksy , A , Matthews , D , Weinstein , L S , Hahn , H , Gröne , H-J , Graumann , P L , Niessen , C M , Offermanns , S , Wickström , S A & Worzfeld , T 2021 , ' Mechanochemical control of epidermal stem cell divisions by B-plexins ' , Nature Communications , vol. 12 , no. 1 , 1308 . https://doi.org/10.1038/s41467-021-21513-9

Title: Mechanochemical control of epidermal stem cell divisions by B-plexins
Author: Chen Jiang; 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; Wickström, Sara A.; Worzfeld, Thomas
Contributor organization: Helsinki Institute of Life Science HiLIFE
University of Helsinki
Department of Biochemistry and Developmental Biology
STEMM - Stem Cells and Metabolism Research Program
Research Programs Unit
Faculty of Medicine
Date: 2021-02-26
Language: eng
Number of pages: 17
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-21513-9
URI: http://hdl.handle.net/10138/340183
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.
Subject: 1182 Biochemistry, cell and molecular biology
Stem cell mechanics
Plexins
Epidermis
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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