Fig 1.
The Drosophila embryo as a model system for size homeostasis.
(A) Specification of embryonic stages over time; the red boxed region represents the time period of simulations [18]. (B) Summary of genetic perturbations simulated in this study. The wt genotype is engrailed>GAL4, UAS>GFP. The perturbations are crosses between the wt and UAS>CyclinE and UAS>dacapo lines, respectively. (C) Stage 11 embryo expressing GFP in the posterior compartment, stained for DE-cadherin to show cell boundaries. (D) High magnification image of simulation domain. (E, F) Data extracted from [14] demonstrating that compartment dimensions are robust to manipulations that change the number of cells. (G) Cell death, indicated by cleaved Drosophila death caspase-1 (DCP-1) antibody staining [19], is statistically more likely to occur in the front half of the posterior compartment in en>CycE embryos [14].
Fig 2.
Vertex model of posterior compartment dynamics during the last division cycle in the Drosophila embryonic epidermis.
(A) Snapshot of the initial tissue configuration for each simulation, with mechanical parameters in Eq (3) annotated. (B) Schematic diagram of a junctional rearrangement (T1 swap), a cell removal (T2 transition), and cell division in the vertex model. Numbers indicate cell indices. (C) Snapshot of a wt simulation at the final time point, once all cell divisions have occurred, with annotation for the front and back halves of the P compartment. Parameter values are listed in Table 1.
Table 1.
Description of non-dimensionalized parameter values used in our simulations.
Fig 3.
Compartment size control can emerge from passive mechanical forces.
(A) Snapshots of wt, en>dap and en>CycE simulations, each following the final round of division. Parameter values are listed in Table 1. (B) Comparison of simulated P compartment areas and cell numbers with observed values [14]. Mean values from 100 simulations are shown and error bars are standard deviations. (C) Variation of P compartment area (upper row) and cell number (middle row), and of the number of accumulated cell deaths in the en>CycE perturbation over 100 simulations in the front and back halves of the P compartment (lower row), as each mechanical parameter is varied individually, holding all other parameters at their values listed in Table 1. Shaded areas in (B) and (C) mark the ranges of experimentally observed values and are added for reference (see main text for details).
Fig 4.
Spatial regulation of mechanical cell properties can induce asymmetry of cell death occurrence inside posterior compartments.
(A) Schematic of the distinct forms of mechanical asymmetries considered in this work. (B) Snapshot of final configuration of simulations for each considered perturbation. (C) Comparison of P compartment areas and cell numbers for each of the considered perturbations with experimental values. Mean values from 100 simulations are shown and error bars are standard deviations. Parameter values are given in Table 1 and in the main text. Shaded areas mark the ranges of experimentally observed values and are added for reference and comparison with Fig 3, S1 and S2 Figs. (D) Comparison of accumulated number cell deaths over 100 simulations in the front and back halves of the P compartment for each of the considered perturbations.
Fig 5.
Sensitivity of P compartment size and cell number to asymmetry.
Variation of P compartment area (upper row) and cell number (middle row), and of the number of accumulated cell deaths over 100 simulations in the front and back halves of the P compartment (lower row), as the asymmetry parameters λA, λl, and λp are varied individually while holding all other parameters at their values listed in Table 1. Shaded areas are added for comparison with Figs 3 and 5.
Fig 6.
Differential growth and mechanical regulation generate distinct distributions of cell shapes.
Distributions of cell areas (row 1), cell perimeters (row 2), cell edge lengths (row 3), and cell elongations (row 4) for the wt simulations of each scenario of cellular asymmetry. We distinguish distributions for all cells in the posterior compartment (‘All’), for cells the cells in the front half (‘Front’), and cells the back half (‘Back’).
Fig 7.
Cell area distributions in the en>dap and en>CycE perturbations are multimodal.
Distributions of cell areas for each perturbation of cell division events (wt, en>dap and en>CycE) and each scenario of cellular asymmetry. Cell areas are recorded at the end of each simulation and error bars denote standard deviations across 100 simulations. Parameter values are given in Table 1 and in the main text.
Fig 8.
Simulated laser ablation experiments allow discrimination between asymmetry scenarios.
Average initial vertex recoil velocities and total recoil distances across simulations of wt and perturbations. Error bars denote standard deviations across 100 simulations. Parameter values are given in Table 1 and in the main text.