Jolly, Mohit KumarBoareto, MarceloLu, MingyangOnuchic, José NelsonClementi, CeciliaBen-Jacob, Eshel2015-07-092015-07-092015Jolly, Mohit Kumar, Boareto, Marcelo, Lu, Mingyang, et al.. "Operating principles of Notch–Delta–Jagged module of cell–cell communication." <i>New Journal of Physics,</i> 17, (2015) IOP Publishing: 55021. http://dx.doi.org/10.1088/1367-2630/17/5/055021.https://hdl.handle.net/1911/80851Notch pathway is an evolutionarily conserved cell–cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand—Delta or Jagged—of another cell. Notch–Delta (ND) signaling forms a two-way switch, and two cells interacting via ND signaling adopt different fates—Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Notch–Delta–Jagged signaling (NDJ) behaves as a three-way switch and enables an additional fate—hybrid Sender/Receiver (S/R) (medium ligand, medium receptor). Here, by extending our framework of NDJ signaling for a two-cell system, we show that higher production rate of Jagged, but not that of Delta, expands the range of parameters for which both cells attain the hybrid S/R state. Conversely, glycosyltransferase Fringe and cis-inhibition reduces this range of conditions, and reduces the relative stability of the hybrid S/R state, thereby promoting cell-fate divergence and consequently lateral inhibition-based patterns. Lastly, soluble Jagged drives the cells to attain the hybrid S/R state, and soluble Delta drives them to be Receivers. We also discuss the critical role of hybrid S/R state in promoting cancer metastasis by enabling collective cell migration and expanding cancer stem cell (CSC) population.engContent from this work may be used under the terms of the Creative Commons Attribution 3.0 licenceJournal articlehttp://dx.doi.org/10.1088/1367-2630/17/5/055021