Planar polarization of the atypical myosin Dachs orients cell divisions in Drosophila

Abstract

Tissues can grow in a particular direction by controlling the orientation of cell divisions. This phenomenon is evident in the developing Drosophila wing epithelium, where the tissue becomes elongated along the proximal-distal axis. We show that orientation of cell divisions in the wing requires planar polarization of an atypical myosin, Dachs. Our evidence suggests that Dachs constricts cell-cell junctions to alter the geometry of cell shapes at the apical surface, and that cell shape then determines the orientation of the mitotic spindle. Using a computational model of a growing epithelium, we show that polarized cell tension is sufficient to orient cell shapes, cell divisions, and tissue growth. Planar polarization of Dachs is ultimately oriented by long-range gradients emanating from compartment boundaries, and is therefore a mechanism linking these gradients with the control of tissue shape.

Mechanisms and mechanics of cell competition in epithelia

“…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.…”

“…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).…”

Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis

“…Cell division has been suggested to participate in this feedback (10) because the rate of animal cell proliferation responds to changes in extrinsic forces in several experimental settings (9). Further, division makes an important contribution to tissue morphogenesis in animals (11,12), accounts for much of the topological disorder observed in epithelia (13), can drive tissue elongation (10), and can facilitate the return to homeostatic cell packing following a deformation (2). Importantly, for each of these functions, the impact of cell division depends critically on the orientation of divisions.…”

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

“…154 Moreover, members of the Hippo pathway are important to orient the plane of cell division in certain tissues such as in the developing kidney. 155,156 In addition, upstream regulators of the Hippo/Yap pathway such as the tumor suppressor LKB1, 157,158 AMPK 159 and TAO1 kinase 160,161 are involved in spindle orientation. The connections between AJs and Hippo/Yap1 have been observed in several contexts.…”