Linking chemical signaling to mechanical components to determine tissue shape in the Drosophila wing imaginal disc

Abstract

During organogenesis in the Drosophila wing imaginal disc, the regulation of epithelial cell height and curvature is crucial in developing correct tissue shapes. This requires the interplay between mechanical forces and morphogen-mechanogen pathways, at both the cell and tissue levels. Morphogens, such as Decapentaplegic (Dpp), regulate cell growth and division, as well as mechanogen activity. Mechanogens, such as RhoGTPases, are small diffusible molecules that regulate mechanical components, such as actin and myosin, to coordinate cell shape and tissue geometry. Even though the effect of morphogens in regulating mechanogens is critical for proper tissue formation, insufficient work has been done to understand this in the context of epithelial organogenesis. In this study, a combination of experimental and mathematical modeling approaches are used to study the linkage between Dpp and Rho1, Cdc42 in the wing imaginal disc. By using experiments, a new regulation between Dpp/pMad and Cdc42 has been identified, as well as the interaction between Cdc42 and Rho1. A mathematical model has been developed by using a system of reaction-diffusion equations to model Dpp, Rho1, and Cdc42 dynamics, as well as the newly identified regulations. In particular, the signaling model uses a discrete node structure from a multi-scale subcellular element model. We apply this model to investigate the robustness of the proposed networks, in addition to the effect of tissue geometry on the concentration profiles of both the morphogens and mechanogens.