A computational model predicts genetic nodes that allow switching between species-specific responses in a conserved signaling network

摘要: Cell signaling networks regulate a variety of developmental and physiological processes, changes in their response to external stimuli are often implicated disease initiation progression. To elucidate how different responses can arise from conserved networks, we have developed mathematical model the well-characterized Caenorhabditis vulval development network involving EGF, Wnt Notch that recapitulates biologically observed behaviors. We experimentally block specific element EGF pathway (MEK), find behaviors two species, C. elegans briggsae. When separate our parameters into subsets correspond these responses, they yield consistent with experimental results, despite initial parameter grouping based on perturbation single node pathway. Finally, analysis predicts may be critical for theoretically differences, suggesting modifications might allow intentional switching between species' responses. Our results indicate all manipulations within signal transduction do not same outcome, provide framework identify genetic perturbations will confer unique network.