(636f) Quantitative Analysis of EGFR-Regulated Size Control in the Drosophila Epidermis

Programmed cell death (apoptosis) plays multiple fundamental roles in organogenesis and tissue homeostasis, including the regulation of compartment size and shape. To better understand the patterning and size control functions of apoptosis, we are using high-resolution confocal microscopy and an in-house image-processing pipeline to quantify the effect of epidermal growth factor receptor (EGFR) signaling on cell topology and cell death in the Drosophila embryonic epidermis. Past genetic studies have firmly established he importance of apoptosis in development. However, due to the transient nature of apoptosis, few attempts have been made to quantitatively characterize the cellular processes that regulate it. We are developing quantitative approaches toward using cellular-resolution data of the EGFR gradient in embryonic stages 8-13 to inform a computational model of the epidermis that includes intracellular signaling and cell mechanics. The integrated model incorporates both a vertex-based description of cellular mechanics and an independent reaction-diffusion description of the EGFR gradient in the developing epithelium. A systematic framework for modeling these core processes lends insight into the strategies employed during development to generate tissues of the correct size and shape. This model can also provide key insights into diseases that result from the dysregulation of apoptosis, such as cancer.