Jiang, Chen ORCID: 0000-0002-0010-0402, Javed, Ahsan ORCID: 0000-0003-2950-7297, Kaiser, Laura ORCID: 0000-0002-3212-576X, Nava, Michele M., Xu, Rui, Brandt, Dominique T., Zhao, Dandan, Mayer, Benjamin, Fernandez-Baldovinos, Javier, Zhou, Luping, Hoess, Carsten, Sawmynaden, Kovilen, Oleksy, Arkadiusz, Matthews, David, Weinstein, Lee S., Hahn, Heidi, Groene, Hermann-Josef, Graumann, Peter L., Niessen, Carien M. ORCID: 0000-0002-4892-9391, Offermanns, Stefan, Wickstroem, Sara A. and Worzfeld, Thomas (2021). Mechanochemical control of epidermal stem cell divisions by B-plexins. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jiang, ChenUNSPECIFIEDorcid.org/0000-0002-0010-0402UNSPECIFIED
Javed, AhsanUNSPECIFIEDorcid.org/0000-0003-2950-7297UNSPECIFIED
Kaiser, LauraUNSPECIFIEDorcid.org/0000-0002-3212-576XUNSPECIFIED
Nava, Michele M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, RuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandt, Dominique T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, DandanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Baldovinos, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, LupingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoess, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sawmynaden, KovilenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oleksy, ArkadiuszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matthews, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weinstein, Lee S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groene, Hermann-JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graumann, Peter L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niessen, Carien M.UNSPECIFIEDorcid.org/0000-0002-4892-9391UNSPECIFIED
Offermanns, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wickstroem, Sara A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worzfeld, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-600102
DOI: 10.1038/s41467-021-21513-9
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60010

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