Mechanochemical control of epidermal stem cell divisions by B-plexins.
Animals
Carcinoma, Basal Cell
/ pathology
Carrier Proteins
/ metabolism
Cell Adhesion
Cell Adhesion Molecules
/ metabolism
Cell Division
/ physiology
Cell Proliferation
Embryonic Development
/ physiology
Epidermal Cells
/ metabolism
Epithelial Cells
/ metabolism
Epithelium
/ metabolism
Female
Intercellular Junctions
Keratinocytes
Mice
Mitosis
Morphogenesis
Nerve Tissue Proteins
/ metabolism
Organogenesis
Receptors, Cell Surface
/ metabolism
Stem Cells
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 02 2021
26 02 2021
Historique:
received:
24
04
2020
accepted:
28
01
2021
entrez:
27
2
2021
pubmed:
28
2
2021
medline:
16
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33637728
doi: 10.1038/s41467-021-21513-9
pii: 10.1038/s41467-021-21513-9
pmc: PMC7910479
doi:
Substances chimiques
Carrier Proteins
0
Cell Adhesion Molecules
0
Nerve Tissue Proteins
0
PLXNB1 protein, human
0
PLXNB2 protein, human
0
Receptors, Cell Surface
0
plexin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1308Références
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