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The expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is still poorly understood. Using the Drosophila pupal notum, a single layer epithelium where extrusions are caspase-dependent, we showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration and dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion, while microtubule stabilisation strongly impairs cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting step of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation., (© 2022. The Author(s).)

Cell extrusion is a highly coordinated process allowing the removal of an epithelial cell from the tissue layer without disrupting its integrity. Two new studies shed new light on the complexity of cell-cell coordination at play during cell extrusion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Actomyosin flows are involved in a variety of cellular processes, including cytokinesis, cell migration, polarization, and morphogenesis. In epithelia, flow polarization orients cell deformations. It is unclear, however, how flows are polarized and how global patterns of junction remodeling emerge from flow polarization locally. We address this question during intercalation-driving extension of the Drosophila germband. Intercalation is associated with polarized junction remodeling, whereby actomyosin pulses flow anisotropically toward dorsal-ventral junctions and shrink them. Here, we show that planar polarization of flows emerges from polarized fluctuations in the levels of E-cadherin clusters that produce transient and oscillating asymmetries of coupling. These fluctuations are triggered by polarized E-cadherin endocytosis and are amplified by flow itself. This work suggests that fluctuations and mechanical instability are not the consequences of limited control over the systems key parameters, but rather that they define the axis of symmetry breaking., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Cells are active materials; they can change shape using internal energy to build contractile networks of actin filaments and myosin motors. Contractility of the actomyosin cortex is tightly regulated in space and time to orchestrate cell shape changes. Conserved biochemical pathways regulate actomyosin networks in subcellular domains which drive cell shape changes. Actomyosin networks display complex dynamics, such as flows and pulses, which participate in myosin distribution and provide a more realistic description of the spatial distribution and evolution of forces during morphogenesis. Such dynamics are influenced by the mechanical properties of actomyosin networks. Moreover, actomyosin can self-organize and respond to mechanical stimuli through multiple types of biomechanical feedback. In this review we propose a framework encapsulating spatiotemporal regulation of contractility from established pathways with the dynamics and mechanics of actomyosin networks. Through the comparison of cytokinesis, cell migration and epithelial morphogenesis, we delineate emergent properties of contractile activity, including self-organization, adaptability and robustness. [ABSTRACT FROM AUTHOR]

E-cadherin plays a pivotal role in epithelial morphogenesis. It controls the intercellular adhesion required for tissue cohesion and anchors the actomyosin-driven tension needed to change cell shape. In the early Drosophila embryo, Myosin-II (Myo-II) controls the planar polarized remodelling of cell junctions and tissue extension. The E-cadherin distribution is also planar polarized and complementary to the Myosin-II distribution. Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis. Blocking E-cadherin endocytosis resulted in cell intercalation defects. We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin. This requires the concerted action of the formin Diaphanous (Dia) and Myosin-II. Their activity is controlled by the guanine exchange factor RhoGEF2, which is planar polarized and absent in non-intercalating regions. Finally, we provide evidence that Dia and Myo-II control the initiation of E-cadherin endocytosis by regulating the lateral clustering of E-cadherin. [ABSTRACT FROM AUTHOR]