Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary

Abstract

Subdividing proliferating tissues into compartments is an evolutionarily conserved strategy of animal development [1-6]. Signals across boundaries between compartments can result in local expression of secreted proteins organizing growth and patterning of tissues [1-6]. Sharp and straight interfaces between compartments are crucial for stabilizing the position of such organizers and therefore for precise implementation of body plans. Maintaining boundaries in proliferating tissues requires mechanisms to counteract cell rearrangements caused by cell division; however, the nature of such mechanisms remains unclear. Here we quantitatively analyzed cell morphology and the response to the laser ablation of cell bonds in the vicinity of the anteroposterior compartment boundary in developing Drosophila wings. We found that mechanical tension is approximately 2.5-fold increased on cell bonds along this compartment boundary as compared to the remaining tissue. Cell bond tension is decreased in the presence of Y-27632 [7], an inhibitor of Rho-kinase whose main effector is Myosin II [8]. Simulations using a vertex model [9] demonstrate that a 2.5-fold increase in local cell bond tension suffices to guide the rearrangement of cells after cell division to maintain compartment boundaries. Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries.

Mechanisms and mechanics of cell competition in epithelia

“…This could explain why the influence of cell competition does not cross the boundary that separates the anterior and posterior compartment in D. melanogaster imaginal discs. As this boundary is characterized by increased junctional tension 84 , it could act as a mechanical insulator, thus preventing transmission of the strains caused by inhomogeneous growth. Mechanical influences could also explain how cells, such as cancer cells, that acquire extra DNA or chromosomes could become super-competitors, as these cells tend to increase in size as a result of hyperploidy 85 .…”

“…Another limitation of most current vertex models is that they are restricted to two dimensions, although recent work suggests that three-dimensional modelling is possible 91 . Despite these simplifications, vertex models have successfully represented biologically relevant processes 77,84,88,89,92 . Nevertheless, there is a need for validation with experimental measurements of forces within tissues.…”

“…Nevertheless, there is a need for validation with experimental measurements of forces within tissues. The most successful approach so far involves ablating individual junctions with an infrared laser and inferring the tension from the initial speed of vertex recoil 81,84 . Because this method is invasive and samples only a small number of junctions, alternative approaches are needed.…”

“…Examples of the second approach are vertex models that consider cells as individual objects 82 . They are increasingly used to study cellular processes within epithelia, including cell motility, cell-cell adhesion, mitosis, delamination and apoptosis 77,84,88,89 . As currently implemented, these models share the key assumption that epithelial mechanics are dominated by forces acting within the plane of cellular junctions (adherens junctions).…”

Impact of implementation choices on quantitative predictions of cell-based computational models

“…Vertex models have been used to study a variety of processes in epithelial tissues [3][4][5][6][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. These processes include growth of the Drosophila wing imaginal disc [3,4], migration of the visceral endoderm of mouse embryos [5], and tissue size control in the Drosophila embryonic epidermis [31].…”