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

## TL;DR

This paper introduces a mathematical model to study how signals are distributed during egg development in fruit flies, focusing on the interaction between cells and how their movement affects signaling.

## Contribution

The paper introduces a novel mathematical framework to model the dynamic distribution of signaling molecules during Drosophila oogenesis.

## Key findings

- The model captures GRK diffusion and EGFR activation in follicle cells during oocyte growth.
- Perturbations in egg chamber morphology affect EGFR signaling distribution.
- Follicle cell and oocyte movement contributes to EGFR signaling activation patterns.

## 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.

Cell differentiation is a key process in an organism’s development, and it relies on spatiotemporal information provided by the anisotropic and time-dependent distribution of signals. For this reason, understanding the pattern formation of signal within a growing organism is central to understanding cell differentiation, which in turn leads to organ formation. Drosophila oogenesis serves as a model framework to study the coordination of many processes, including cell migration, diffusion of signal, and reaction pathways within the cells. However, isolating each of these mechanisms to understand its role in this complex interaction can be difficult, or even unfeasible, from an experimental point of view, because of the lethality of some perturbations. To overcome this limitation, we propose a comprehensive mathematical model which includes the interacting pieces, and which can serve as a complementary tool to understand the role of each mechanism in the global pattern formation via numerical simulations.