PT  - JOURNAL ARTICLE
AU  - Lisa Donker
AU  - Marjolein J. Vliem
AU  - Helena Canever
AU  - Manuel Gómez-González
AU  - Miquel Bosch-Padrós
AU  - Willem-Jan Pannekoek
AU  - Xavier Trepat
AU  - Nicolas Borghi
AU  - Martijn Gloerich
TI  - A mechanical G2 checkpoint controls epithelial cell division through E-cadherin-mediated regulation of Wee1-Cdk1
AID  - 10.1101/2021.11.29.470352
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.29.470352
4099  - http://biorxiv.org/content/early/2021/11/29/2021.11.29.470352.short
4100  - http://biorxiv.org/content/early/2021/11/29/2021.11.29.470352.full
AB  - Epithelial cell divisions must be tightly coordinated with cell loss to preserve epithelial integrity. However, it is not well understood how the rate of epithelial cell division adapts to changes in cell number, for instance during homeostatic turnover or upon wounding of epithelia. Here, we show epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell cycle progression. We demonstrate that tensile forces on E-cadherin adhesions are reduced as local cell density increases, which prompts the accumulation of the G2 checkpoint kinase Wee1. This elevated abundance of Wee1 results in inhibitory phoshorylation of Cdk1, and thereby establishes a pool of cells that is temporarily halted in G2-phase. Importantly, these cells are readily triggered to divide upon epithelial wounding, due to the consequent increase in intercellular forces and resulting degradation of Wee1. Our data thus demonstrate that epithelial cell division is controlled by a mechanical G2 checkpoint, which is regulated by cell density-dependent intercellular forces sensed and transduced by E-cadherin adhesions.Competing Interest StatementThe authors have declared no competing interest.