Many epithelial tissues pack cells into a honeycomb pattern to support their structural and functional integrity. Developmental changes in cell packing geometry have been shown to be regulated by both mechanical and biochemical interactions between cells; however, it is largely unknown how molecular and cellular dynamics and tissue mechanics are orchestrated to realize the correct and robust development of hexagonal cell packing. Here, by combining mechanical and genetic perturbations along with live imaging and Bayesian force inference, we investigate how mechanical forces regulate cellular dynamics to attain a hexagonal cell configuration in the Drosophila pupal wing. We show that tissue stress is oriented towards the proximal-distal axis by extrinsic forces acting on the wing. Cells respond to tissue stretching and orient cell contact surfaces with the stretching direction of the tissue, thereby stabilizing the balance between the intrinsic cell junction tension and the extrinsic force at the cell-population level. Consequently, under topological constraints of the two-dimensional epithelial sheet, mismatches in the orientation of hexagonal arrays are suppressed, allowing more rapid relaxation to the hexagonal cell pattern. Thus, our results identify the mechanism through which the mechanical anisotropy in a tissue promotes ordering in cell packing geometry.
AIP1 and cofilin ensure a resistance to tissue tension and promote directional cell rearrangement
In order to understand how tissue mechanics shapes animal body, it is critical to clarify how cells respond to and resist tissue stress when undergoing morphogenetic processes such as cell rearrangement. Here, we address the question in the Drosophila wing epithelium, where anisotropic tissue tension orients cell rearrangements. We found that anisotropic tissue tension localizes actin interacting protein 1 (AIP1), a cofactor of cofilin, on the remodeling junction via cooperative binding of cofilin to F-actin. AIP1 and cofilin promote actin turnover and locally regulate the Canoe-mediated linkage between actomyosin and the junction. This mechanism is essential for cells to resist the mechanical load imposed on the remodeling junction perpendicular to the direction of tissue stretching. Thus, the present study delineates how AIP1 and cofilin achieve an optimal balance between resistance to tissue tension and morphogenesis.
Kaoru Sugimura and Shuji Ishihara. The mechanical anisotropy in a tissue promotes ordering in hexagonal cell packing. Development 140: 4091-4101 (2013) [Journal][In this issue]
Keisuke Ikawa and Kaoru Sugimura. AIP1 and cofilin ensure a resistance to tissue tension and promote directional cell rearrangement. Nature Communications 9: 3295 (2018). [Journal][Press release]