Multicellular organization by a non-diffusible signal: Mathematical and experimental analysis of morphogenetic cell movements in myxobacteria

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One of the essential problems in developmental biology is how spatial patterns of differentiated cells (e.g. tissues) can arise from an initially uniform mass of identical cells. Here, a unique group of biologists, mathematicians and physicists addresses this question using multicellular development in Myxococcus xanthus as a model system. The working group will apply a highly interdisciplinary approach combining biological experiments with quantitative mathematical modeling and simulation. In response to starvation, cells of the gliding bacterium M. xanthus initiate a multicellular developmental program that leads to streaming and aggregation patterns and culminates in the formation of spore-filled fruiting bodies. The non-diffusible C-signal plays a key role in inducing and choreographing the aggregation and sporulation processes. The main objective of this proposal is the construction and analysis of a quantitative mathematical model for the development of a three-dimensional fruiting body starting from individual cells. The mathematical model will allow us to investigate, whether the cell surface-associated C-signal is sufficient for explaining the multicellular organization of myxobacteria or if additional signaling mechanisms are required (e.g. a diffusive signaling mechanism, which plays a key role in the multicellular organization of the slime mould Dictyostelium discoideum). Model predictions will be validated in experiments with developmental mutants in which C-signaling is deficient. This project promises new insights into pattern formation mechanisms in biological systems and a better understanding of how non-diffusible morphogens may induce and organize morphogenetic cell movements.