A Chemical-mechanical Coupled Model Predicts Roles of Spatial Distribution of Morphogen in Maintaining Tissue Growth

Abstract

The exact mechanism controlling cell growth remains a grand challenge in developmental biology and regenerative medicine. The Drosophila wing disc tissue serves as an ideal biological model to study growth regulation due to similar features observed in other developmental systems. The mechanism of growth regulation in the wing disc remains a subject of intense debate. Most existing models to study tissue growth focus on either chemical signals or mechanical forces only. Here we developed a multiscale chemical-mechanical coupled model to test a growth regulation mechanism depending on the spatial range of the morphogen gradient. By comparing the spatial distribution of cell division and the overall shape of tissue obtained in the coupled model with experimental data, our results show that the distribution of the Dpp morphogen can be critical in resulting tissue size and shape. A larger tissue size with a faster growth rate and more symmetric shape can be achieved if the Dpp gradient spreads in a larger domain. Together with the absorbing boundary conditions, the feedback regulation that downregulates Dpp receptors on the cell membrane allows the further spread of the morphogen away from its source region, resulting in prolonged tissue growth at a more spatially homogeneous growth rate. Summary StatementA multiscale chemical-mechanical model was developed by coupling submodels representing dynamics of a morphogen gradient at the tissue level, intracellular chemical signals, and mechanical properties at the subcellular level. By applying this model to study the Drosophila wing disc, it was found that the spatial range of the morphogen gradient affected tissue growth in terms of the growth rate and the overall shape.