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Citation
Mbodj, A., Gustafson, E.H., Ciglar, L., Junion, G., Gonzalez, A., Girardot, C., Perrin, L., Furlong, E.E., Thieffry, D. (2016). Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes.  PLoS Comput. Biol. 12(9): e1005073.
FlyBase ID
FBrf0233418
Publication Type
Research paper
Abstract

Given the complexity of developmental networks, it is often difficult to predict the effect of genetic perturbations, even within coding genes. Regulatory factors generally have pleiotropic effects, exhibit partially redundant roles, and regulate highly interconnected pathways with ample cross-talk. Here, we delineate a logical model encompassing 48 components and 82 regulatory interactions involved in mesoderm specification during Drosophila development, thereby providing a formal integration of all available genetic information from the literature. The four main tissues derived from mesoderm correspond to alternative stable states. We demonstrate that the model can predict known mutant phenotypes and use it to systematically predict the effects of over 300 new, often non-intuitive, loss- and gain-of-function mutations, and combinations thereof. We further validated several novel predictions experimentally, thereby demonstrating the robustness of model. Logical modelling can thus contribute to formally explain and predict regulatory outcomes underlying cell fate decisions.

PubMed ID
PubMed Central ID
PMC5012701 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Comput. Biol.
    Title
    PLoS Computational Biology
    Publication Year
    2005-
    ISBN/ISSN
    1553-7358 1553-734X
    Data From Reference