Mbodj2016 - Mesoderm specification during Drosophila development

Mbodj2016 - Mesoderm specification during
Drosophila development

This model is described in the article:

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

Mbodj A, Gustafson EH, Ciglar L,
Junion G, Gonzalez A, Girardot C, Perrin L, Furlong EE, Thieffry
D.
PLoS Comput. Biol. 2016 Sep; 12(9):
e1005073
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.

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MODEL1607310000.
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