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Multi-Scale Computational Model Sheds Light on Embryonic Development

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The delicate cellular process that occurs during somite formation in early embryonic development has come into focus with the help of a computational model. Researchers at Indiana University's Biocomplexity Institute and the University of Arizona have developed a multi-scale mathematical model of somitogenesis by combining a cell-based simulation platform called CompuCell3D with existing models that integrate sub-models of intracellular genetic networks comprising the "segmentation clock," which determines how embryos develop. Their model was described in a PLoS Computational Biology paper in October.

"Building successful multi-scale composite models is challenging because we must first combine the biological sub-models in a biologically consistent way, and then connect the corresponding mathematical sub-models to reflect the biological connection," says Susan Hester, a graduate student at Arizona and co-author of the paper. "In this case, interaction between sub-models entails interaction between different computational methods. So in essence, to connect two sub-models requires an additional model of how they interact at the biological, mathematical, computational, and simulation-abstraction levels."

Using this approach, the researchers were able to model and study somitogenesis in chickens, garden snakes, mice, and zebrafish. But Hester says they could also envision applying their model to the clinic by predicting how certain potential toxins and therapies may affect human embyronic development. "Understanding the multi-scale effects of intervention on a molecular scale will also be necessary for assessing potential early prenatal therapies for genetic developmental defects," she says. "Because somitogenesis involves interactions between many scales as well as coordination between events occurring in time and space, it serves as both a uniquely interesting area of study in its own right and a case study for the development of predictive and informative multi-scale models."

Hester and her colleagues hope that the groundwork they've laid with this initial effort will allow them to use their model to perform more focused explorations of mechanisms important for somitogenesis. "The next generation of our integrated model will include sub-models for retinoic acid production as well as sub-models of the interactions between modeled morphogens," she says. This may allow them to gain insight into how groups of cells determine gene expression in the anterior presomatic mesoderm, in the heart. Also in the works is the extension of their model into three dimensions to better examine the structure of somites as they form.

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