Landino Jennifer, Misterovich Eileen, van den Goor Lotte, Adhikary Babli, Chumki Shahana, Davidson Lance A, Miller Ann L
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Dev Cell. 2025 Apr 8. doi: 10.1016/j.devcel.2025.03.010.
Cytokinesis challenges epithelial tissue homeostasis by generating forces that pull on neighboring cells. Junction reinforcement at the furrow in Xenopus epithelia regulates the speed of furrowing, suggesting that cytokinesis is subject to resistive forces from epithelial neighbors. We show that contractility factors accumulate near the furrow in neighboring cells, and increasing neighbor cell stiffness slows furrowing. Optogenetically increasing contractility in one or both neighbor cells slows furrowing or induces cytokinetic failure. Uncoupling mechanotransduction between dividing cells and their neighbors increases the furrow ingression rate, alters topological cell packing following cytokinesis, and impairs barrier function at the furrow. Computational modeling validates our findings and provides additional insights about epithelial mechanics during cytokinesis. We conclude that forces from the cytokinetic array must be carefully balanced with restraining forces generated by neighbor cells to regulate the speed and success of cytokinesis and maintain epithelial homeostasis.
胞质分裂通过产生牵拉相邻细胞的力来挑战上皮组织的稳态。非洲爪蟾上皮细胞沟处的连接增强调节沟陷的速度,这表明胞质分裂受到来自上皮邻居的阻力。我们发现收缩因子在相邻细胞的沟附近积累,增加相邻细胞的硬度会减缓沟陷。通过光遗传学增加一个或两个相邻细胞的收缩性会减缓沟陷或导致胞质分裂失败。将分裂细胞与其邻居之间的机械转导解偶联会增加沟的内陷率,改变胞质分裂后的拓扑细胞排列,并损害沟处的屏障功能。计算模型验证了我们的发现,并提供了关于胞质分裂过程中上皮力学的更多见解。我们得出结论,胞质分裂阵列产生的力必须与相邻细胞产生的约束力仔细平衡,以调节胞质分裂的速度和成功率,并维持上皮稳态。