Abstract
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.
Highlights
Epithelial patterning, in which cells assume required positions within emerging epithelia, is essential to the development of all animals
Organs are assembled through a complex combination of cell proliferation, programmed cell death, cell movements, etc
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 largescale patterns necessary to create a useful organ
Summary
Epithelial patterning, in which cells assume required positions within emerging epithelia, is essential to the development of all animals. Mathematical models and computer simulations of these processes based on local reduction of free-energy can replicate experimentally observed cell shapes within epithelia as diverse as embryonic germ layers and Drosophila ommatidial patterns [3,4,5,6,7,8]. These models do not address cell placement, which commonly plays a key role in producing functional tissues for example in the mammalian and insect retinas [9,10]. We proposed that multiple adhesion molecules expressed in precise spatial patterns can generate more complex patterns via local energy minimization [11] Such models self-organize based on a small number of cell and global properties. We did not verify that such forces could control the arrangement of cells in a complex pattern [11]
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