A computational framework to study EGFR signaling distribution in egg chambers during dynamic interactions between soma and germline

Abstract

Forming organs requires the appropriate distribution of spatiotemporal signals leading to tissue patterning and morphogenesis. Advances in genetic tools contributed to our understanding of cell signaling and their associated genes. Yet, due to technical challenges, the contribution of dynamic morphological transformations of tissues during organ formation remains widely unexplored. Here, we develop a new mathematical approach to understand the variables that shape the dynamic distribution of ligand and signaling. We use the TGF-α-like ligand Gurken (GRK) and the activation of the epidermal growth factor receptor (EGFR) during Drosophila oogenesis to build the model. Our model accounts for GRK secretion from a moving source, its diffusion in the perivitelline space, and the activation of EGFR in the overlaying follicle cells. Furthermore, we also capture the rapid growth of the oocyte, which was a major challenge to integrate into a model. We modeled the dynamic distribution of GRK and EGFR activation by a series of mathematical equations. We used this model to study how perturbations of the egg chamber's morphological evolution impact cell signaling, which could not be achieved via genetic perturbation. We found that the relative movement of the follicle cells and the oocyte contributes to the distribution of EGFR signaling activation.