The Interaction of Mechanics and the Hippo Pathway in Drosophila melanogaster

SIMPLE SUMMARY: Control of tissue growth is an important component of cancer treatment, but understanding how to do this effectively is still in the early stages. Tissue growth typically involves both complex interacting signal transduction networks as well as mechanical interactions within and between cells, and how they interact to control growth is an open problem. Herein we begin the process of how to understand the interactions by focusing on tissue growth in the fruit fly Drosophila melanogaster. A model of the Hippo pathway, which is one of the primary growth-control pathways, is integrated with a description of the mechanical behavior of cells in wing-disc tissue to predict how mechanics and signaling interact, and a number of significant insights and predictions have emerged from the analysis of the model. ABSTRACT: Drosophila melanogaster has emerged as an ideal system for studying the networks that control tissue development and homeostasis and, given the similarity of the pathways involved, controlled and uncontrolled growth in mammalian systems. The signaling pathways used in patterning the Drosophila wing disc are well known and result in the emergence of interaction of these pathways with the Hippo signaling pathway, which plays a central role in controlling cell proliferation and apoptosis. Mechanical effects are another major factor in the control of growth, but far less is known about how they exert their control. Herein, we develop a mathematical model that integrates the mechanical interactions between cells, which occur via adherens and tight junctions, with the intracellular actin network and the Hippo pathway so as to better understand cell-autonomous and non-autonomous control of growth in response to mechanical forces.