Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes

We delineate a logical model encompassing 48 components and 82 regulatory interactions controlling mesoderm specification during Drosophila development, thereby integrating all major genetic processes underlying the formation of four mesodermal tissues. The model is based on in vivo genetic data, partly confirmed by functional genomic data.

Model simulations qualitatively recapitulate the expression of the main lineage markers of each mesodermal derivative, from developmental stage 8 to 10, for the wild type case, as well as for over twenty reported mutant genotypes.

We further use this model to systematically predict the effects of over 300 loss- and gain-of-function mutations, and combinations thereof. By generating specific mutant combinations, we validated several novel predictions experimentally demonstrating the robustness of model.

This modelling study is the first to tackle the regulatory network controlling the specification of mesoderm during Drosophila development, and more broadly deals with one of the most comprehensive developmental networks that have been modelled to date.