TY - JOUR T1 - Diversity of fate outcomes in cell pairs under lateral inhibition JF - bioRxiv DO - 10.1101/032078 SP - 032078 AU - Nara Guisoni AU - Rosa Martinez Corral AU - Jordi Garcia Ojalvo AU - Joaquín de Navascués Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/11/17/032078.abstract N2 - Cell fate decision making mediated by lateral inhibition via Notch/Delta signalling has been extensively studied, both experimentally and theoretically. Most formalised models consider Notch-Delta interactions among many cells, usually in periodic arrangements, with parameters leading to a dynamical behaviour that typically results in symmetry breaking of signalling states between neighbouring cells. This leads to patterns of sparse cells with distinct fates, whose relative spacing is a measure of the developmental output. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of Notch/Delta signalling can lead to stable symmetric states, with either the two cells activating the Notch receptor, or both expressing the Delta ligand. This model is directly relevant to the regulation of adult stem cell fate, which is often determined by Notch/Delta interactions. We apply this model to the homeostatic replacement of the adult Drosophila intestine, where the fate outcome of intestinal stem cell (ISC) division is stochastic but dependent on the Notch/Delta pathway. Our experiments show a correlation between cellular fate in pairs of progenitor cells and the contact area between them. We interpret this behaviour in terms of the bifurcation properties of our model in the presence of population variability in signalling thresholds. Our results suggest that the dynamics of Notch/Delta signalling can contribute to explain the stochastic balance of cell fate decisions after ISC division, and that the standard model for lateral inhibition is able to account for a wider range of developmental outcomes than checkerboard-like patterning. ER -