Computer Simulation of Cellular Patterning Within the Drosophila Pupal Eye

We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD) as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier–Graner–Hogeweg model (GGH) for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo.Author Summary: During development, organs are assembled through a complex combination of cell proliferation, programmed cell death, cell movements, etc. These aspects of tissue maturation must be achieved with a limited gene set—to achieve complexity, tissues utilize patterning mechanisms. That is, “rules” are used to create heterogeneity in initially homogeneous cell populations. A large number of genes and cell biology mechanisms have been uncovered that mediate this process but we have a limited understanding of how these factors act together to generate the large-scale patterns necessary to create a useful organ. Here, we combine computational modeling with in situ experiments in the developing Drosophila eye to explore these issues. Computer modeling is often criticized for describing known outcomes. We demonstrate how the Glazier–Graner–Hogeweg model can successfully predict surprising outcomes contradictory to models that emerged from our previous studies. We then validated these predictions in the developing eye. These mechanisms, which include the importance of dynamic nuclear movements, may prove generally important in directing cells into their proper niches as developing epithelia mature.