Interplay between the Dividing Cell and Its Neighbors Regulates Adherens Junction Formation during Cytokinesis in Epithelial Tissue

Abstract

How adherens junctions (AJs) are formed upon cell division is largely unexplored. Here, we found that AJ formation is coordinated with cytokinesis and relies on an interplay between the dividing cell and its neighbors. During contraction of the cytokinetic ring, the neighboring cells locally accumulate Myosin II and produce the cortical tension necessary to set the initial geometry of the daughter cell interface. However, the neighboring cell membranes impede AJ formation. Upon midbody formation and concomitantly to neighboring cell withdrawal, Arp2/3-dependent actin polymerization oriented by the midbody maintains AJ geometry and regulates AJ final length and the epithelial cell arrangement upon division. We propose that cytokinesis in epithelia is a multicellular process, whereby the cooperative actions of the dividing cell and its neighbors define a two-tiered mechanism that spatially and temporally controls AJ formation while maintaining tissue cohesiveness.

Cytokinesis in Animal Cells

“…(4) Much of the work on cytokinetic mechanisms in mammals has focused on the analysis of cultured cells grown on artificial surfaces. Recent work in Drosophila has highlighted the importance of extrinsic forces and neighboring cells for cytokinesis in epithelial layers (Founounou et al 2013;Guillot and Lecuit 2013;Herszterg et al 2013;Moraisde-Sa and Sunkel 2013). In the future, it will be exciting to expand cytokinesis research also to mammalian multicellular systems or models.…”

Asymmetric Flows in the Intercellular Membrane during Cytokinesis

“…1). The fold thus consists of two double-layer membranes weakly stapled together by adhesion proteins (3,(8)(9)(10). This membrane fold hangs inside the cell like an annular-shaped partition, with the ring at its inner edge.…”

“…These cells divide via a pinch-off configuration, where the cell-cell contact area diminishes gradually (5). In contrast, in confined environments such as during embryo development (6,7) and in epithelial tissues (8)(9)(10), upon cytokinesis, the daughter cells maintain a finite contact area and form a cell-cell interface consisting of two bilayer membranes, each belonging to one daughter cell (11)(12)(13). Formation of the contractile ring and the membrane partition require a supply of actin, myosin, and phospholipids.…”

“…How is the symmetry in the contractile ring broken? In C. elegans one-cell embryos and Drosophila pupal notum (8,10), it was proposed that asymmetric ingression is a result of an asymmetric distribution of anillin and septin, which are major components of the contractile ring. Other mechanisms have been proposed in systems where a symmetric distribution of contractile ring components is observed.…”

Connections between cadherin-catenin proteins, spindle misorientation, and cancer

“…In Drosophila, it has been observed that the levels of AJs are reduced at the cleavage furrow of dividing cells. [70][71][72] However, in mammalian epithelia such as MDCK cells, intestinal crypt cells, or basal progenitor keratinocytes AJs are maintained during this process. 73,74 It will be interesting to explore how this process is regulated in different cell types and tissues, and the implications of adhesion disengagement and the formation of new junctional contacts for the regenerative properties of progenitor cells.…”