A coupled multi-scale mechanochemical computational model of growth regulation in the Drosophila wing disc

How cells proliferate and know when to stop growing is an important question in development biology and medicine. Uncontrolled growth will lead to abnormal development or fatal disease including cancer. The Drosophila wing disc is a classical system used to study this question due to its simplicity and the richness of experimental data. However, the mechanism of growth regulation is still a subject of debate. Multiple hypotheses based on mechanical and/or chemical signaling have been proposed. However, they either lack experimental evidence or cannot account for all observations. We developed a subcellular mechanical model coupled with a 2D chemical signaling network model to test different hypotheses. The mechanical module provides positions and mechanical stress levels of cells to be used by chemical signaling module to direct the growth and division orientation of cells. Simulation results show that a hypothesized temporal Dpp signaling is not sufficient to describe the growth regulation. Low level of signals at the lateral side of the wing disc results in hyperproliferation and synchronized division of cells. We are currently testing role of coupled Wnt and Dpp signaling in achieving homogeneous growth.