The genetic mechanisms that lead to the precise size and pattering of tissues is an important question that has long fascinated researchers. Although the roles of many chemical signaling pathways have been elucidated, much work remains to understand the overall systems-level network that defines how basic cellular logic is determined as a result of both chemical and environmental factors in a tissue. More specifically, the impact of exogenous forces, such as mechanical compression, on the regulation of these genetic mechanisms to effect basic cellular processes such as proliferation and apoptosis remains unresolved. Although the mechanisms of regulation are unknown, mounting experimental evidence has increasingly implicated mechanical forces in the regulation of cell cycle and cell survival. However, probing these relationships experimentally remains problematic, owing to the unique challenges involved in mechanically manipulating tissues both in and ex vivo. Here we describe the fabrication and implementation of a scalable microfluidic culture chip (the Regulated Epithelial Microenvironment Chip) for studying the impact of exogenous forces on development and gene expression in the Drosophila wing imaginal disc. The device consists of individually addressable culture chambers. Each chamber allows control over the chemical perfusion of culture media, in addition to the precise application of compressive forces exerted on the disc via a pneumatically operated membrane on the chamber’s ceiling. Our results demonstrate that Ca2+ signaling is inhibited during mechanical compression, but once compression is removed a Ca2+ wave cascades throughout the disc. This response is dependent on the presence of specific serum conditions indicating synergy between chemical and mechanical factors. The observed wave is also qualitatively similar to observed waves of Ca2+ in vivo that are likely the result of larval motion. A quantitative understanding of how genetic and environmental factors interact is essential to decoding how basic cellular processes are dynamically regulated and can lead to cessation of growth and homeostasis.