Inhomogeneous mechanotransduction defines the spatial pattern of apoptosis-induced compensatory proliferation.

The number of cells in tissues is controlled by cell division and cell death, and its misregulation could lead to pathological conditions such as cancer. To maintain the cell numbers, a cell-elimination process called apoptosis also stimulates the proliferation of neighboring cells. This mechanism, apoptosis-induced compensatory proliferation, was originally described more than 40 years ago. Although only a limited number of the neighboring cells need to divide to compensate for the apoptotic cell loss, the mechanisms that select cells to divide have remained elusive. Here, we found that spatial inhomogeneity in Yes-associated protein (YAP)-mediated mechanotransduction in neighboring tissues determines the inhomogeneity of compensatory proliferation in Madin-Darby canine kidney (MDCK) cells. Such inhomogeneity arises from the non-uniform distribution of nuclear size and the non-uniform pattern of mechanical force applied to neighboring cells. Our findings from a mechanical perspective provide additional insight into how tissues precisely maintain homeostasis.

Author Correction: Basolateral protrusion and apical contraction cooperatively drive Drosophila germ-band extension.

In the version of this Article originally published, the authors cited the wrong articles for reference numbers 18, 30 and 31; the correct ones are listed below. Furthermore, four additional references have been inserted at numbers 37, 38, 39 and 40 as in the list below, and the original references 37-40 have been renumbered. These corrections have been made in the online versions of the Article.

Basolateral protrusion and apical contraction cooperatively drive Drosophila germ-band extension.

Throughout development, tissues undergo complex morphological changes, resulting from cellular mechanics that evolve over time and in three-dimensional space. During Drosophila germ-band extension (GBE), cell intercalation is the key mechanism for tissue extension, and the associated apical junction remodelling is driven by polarized myosin-II-dependent contraction. However, the contribution of the basolateral cellular mechanics to GBE remains poorly understood. Here, we characterize how cells coordinate their shape from the apical to the basal side during rosette formation, a hallmark of cell intercalation. Basolateral rosette formation is driven by cells mostly located at the dorsal/ventral part of the rosette (D/V cells). These cells exhibit actin-rich wedge-shaped basolateral protrusions and migrate towards each other. Surprisingly, the formation of basolateral rosettes precedes that of the apical rosettes. Basolateral rosette formation is independent of apical contractility, but requires Rac1-dependent protrusive motility. Furthermore, we identified Src42A as a regulator of basolateral rosette formation. Our data show that in addition to apical contraction, active cell migration driven by basolateral protrusions plays a pivotal role in rosette formation and contributes to GBE.

Cell Boundary Elongation by Non-autonomous Contractility in Cell Oscillation.

Throughout development, tissues exhibit dynamic cell deformation, which is characterized by the integration of cell boundary contraction and/or elongation. Such changes ultimately establish tissue morphology and function [1-5]. In comparison to cell boundary contraction, which is predominantly driven by non-muscle myosin II (MyoII)-dependent contraction [6-9], the mechanisms of cell boundary elongation remain elusive. We explored the dynamics of the amnioserosa, which is known to exhibit cell shape oscillation [10-15], as a model system to study the subcellular-level mechanics that spatiotemporally evolve during Drosophila dorsal closure. Here we show that cell boundary elongation occurs through a combination of a non-autonomous active process and an autonomous process. The former is driven by a transient change in the level of MyoII in the neighboring cells that pull the vertices, whereas the latter is governed by the relaxation of junctional tension. By monitoring cell boundary deformation during live imaging, junctional tension at the specific phase of cell boundary oscillation, e.g., contraction or elongation, was probed by laser ablation. Junctional tension during boundary elongation is lower than during the other phase of oscillation. We extended our tension measurements to non-invasively estimate a tension map across the tissue, and found a correlation between junctional tension and vinculin dynamics at the cell junction. We propose that the medial actomyosin network is used as an entity to both contract and elongate the cell boundary. Moreover, our findings raise a possibility that the level of vinculin at the cell boundary could be used to approximate junctional tension in vivo.

Epithelial Cell Packing Induces Distinct Modes of Cell Extrusions.

The control of tissue growth, which is a key to maintain the protective barrier function of the epithelium, depends on the balance between cell division and cell extrusion rates [1, 2]. Cells within confluent epithelial layers undergo cell extrusion, which relies on cell-cell interactions [3] and actomyosin contractility [4, 5]. Although it has been reported that cell extrusion is also dependent on cell density [6, 7], the contribution of tissue mechanics, which is tightly regulated by cell density [8-12], to cell extrusion is still poorly understood. By measuring the multicellular dynamics and traction forces, we show that changes in epithelial packing density lead to the emergence of distinct modes of cell extrusion. In confluent epithelia with low cell density, cell extrusion is mainly driven by the lamellipodia-based crawling mechanism in the neighbor non-dying cells in connection with large-scale collective movements. As cell density increases, cell motion is shown to slow down, and the role of a supracellular actomyosin cable formation and its contraction in the neighboring cells becomes the preponderant mechanism to locally promote cell extrusion. We propose that these two distinct mechanisms complement each other to ensure proper cell extrusion depending on the cellular environment. Our study provides a quantitative and robust framework to explain how cell density can influence tissue mechanics and in turn regulate cell extrusion mechanisms.

Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana.

In animals, microtubules and centrosomes direct the migration of gamete pronuclei for fertilization. By contrast, flowering plants have lost essential components of the centrosome, raising the question of how flowering plants control gamete nuclei migration during fertilization. Here, we use Arabidopsis thaliana to document a novel mechanism that regulates F-actin dynamics in the female gametes and is essential for fertilization. Live imaging shows that F-actin structures assist the male nucleus during its migration towards the female nucleus. We identify a female gamete-specific Rho-GTPase that regulates F-actin dynamics and further show that actin-myosin interactions are also involved in male gamete nucleus migration. Genetic analyses and imaging indicate that microtubules are dispensable for migration and fusion of male and female gamete nuclei. The innovation of a novel actin-based mechanism of fertilization during plant evolution might account for the complete loss of the centrosome in flowering plants.