TY - JOUR T1 - Computational Models of the Notch Network Elucidate Mechanisms of Context-dependent Signaling A1 - Agrawal, Smita A1 - Archer, Colin A1 - Schaffer, David V. Y1 - 2009/05/22 N2 - Author Summary The Notch signaling pathway is an evolutionarily conserved signaling system that is involved in various cell fate decisions, both during development of an organism and during adulthood. While the same core circuit functions in various different cellular contexts, it has experimentally been shown to elicit varied behaviors and responses. On the one hand, it functions as a cellular oscillator critical for somitogenesis, whereas in other situations, it can function as a cell fate switch to pattern developing tissue, for example in the Drosophila eye. Furthermore, malfunctioning of Notch signaling is implicated in various cancers. To better understand the underlying mechanisms that allow the network to function distinctly in different contexts, we have mathematically modeled the behavior of the Notch network, encompassing the Notch gene along with two of its downstream effector transcription factors, which together form a network of positive and negative feedback loops. Our results indicate that the qualitative and quantitative behavior of the system can readily be tuned based on key parameters to reflect its multiple roles. Furthermore, our results provide insights into alterations in the signaling system that lead to malfunction and hence disease, which could be used to identify potential drug targets for therapy. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 5 UR - https://doi.org/10.1371/journal.pcbi.1000390 SP - e1000390 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000390 ER -