Regular mosaic pattern development: A study of the interplay between lateral inhibition, apoptosis and differential adhesion

Four different models that interlaced cellular patterning mechanisms in a variety of ways were examined and their output compared to the mosaic of sensory and supporting cells that develops in the chick inner ear sensory epithelium. The results show that: 1) no single patterning mechanism can create a 2-dimensional mosaic pattern of the regularity seen in the chick inner ear; 2) cell death was essential to generate the most regular mosaics, even through extensive cell death has not been reported for the developing basilar papilla; 3) a model that includes an iterative loop of lateral inhibition, programmed cell death and cell rearrangements driven by differential adhesion created mosaics of primary and secondary cells that are more regular than the basilar papilla; 4) this same model was much more robust to changes in homo- and heterotypic cell-cell adhesive differences than models that considered either fewer patterning mechanisms or single rather than iterative use of each mechanism.Patterning the embryo requires collaboration between multiple mechanisms that operate iteratively. Interlacing these mechanisms into feedback loops not only refines the output patterns, but also increases the robustness of patterning to varying initial cell states.Pattern formation is a defining feature of biological development. Many mechanisms account for the emergence of complex patterns within a group of initially equivalent cells, including lateral inhibition, differential adhesion, programmed cell death, cell migration, differential growth, and asymmetric cell division [1]. A rich literature describes computational models of each of these patterning processes and explores how these mechanisms can generate the patterns observed during development [2,3]. These modeling studies have offered invaluable insights. However, the vast majority of earlier computational models have explored the role of individual patterning mechanisms, whereas within the embryo these mechanisms collaborate