Diversity of fate outcomes in cell pairs under lateral inhibition

GUISONI, NARA; DE NAVASCUÉS, JOAQUÍN; MARTINEZ-CORRAL, ROSA; GARCIA-OJALVO, JORDI

Barcelona

Conferencia; International Conference on Systems Biology (ICSB) 2016; 2016

ISSB, CRG, Universitat Pompeu Fabra

Notch/Delta signalling is responsible for cell fate determination in a variety of systems. Typically, Notch activates Delta in the neighbouring cell, where Delta represses Notch. This lateral inhibition mechanism then leads to symmetry breaking of signalling states between neighbouring cells, commonly resulting in salt-and-pepper fate patterns in fields of cells. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of lateral inhibition can lead to stable symmetric signalling states. We apply this model to the adult intestinal stem cell (ISC) of Drosophila, whose fate is stochastic but dependent on the Notch/Delta pathway. Our experiments show a correlation between the signalling state of pairs of cells and the contact area between them. Using our model we interpret this behaviour in terms of the response of the system to population variability in signalling thresholds. Our results suggest that the dynamics of Notch/Delta signalling can contribute to explain stochasticity in stem cell fate decisions, and that the standard model for lateral inhibition can account for a wider range of developmental outcomes than previously considered.