Speaker
Description
Inter-cellular signaling through the Notch receptor plays a central role in a wide range of developmental and physiological processes. In many contexts, signalling-dependent feedback can drive cellular decisions contributing to the regulation of proliferation and differentiation and spatial pattern formation.
In addition to mediating inter-cellular signaling by trans-binding, Notch ligands can also bind Notch on the same cell (cis-binding), sequestering the ligand and receptor in an inactive complex. It has been proposed that this inactive cis-binding can enhance both the speed and regularity of spatial pattern formation by Notch signaling. We have developed a mathematical model to explore the effects of cis-binding on the dynamics of Notch signaling processes. In particular, we focus on the oscillatory transients that have previously been observed in simplified models of Notch signaling. Using linear stability analysis and numerical solutions, we show that these are also present in binding models and that cis-binding can reduce both the amplitude and duration of oscillatory transients. Our results suggest an additional role of cis-binding in regulating the balance between oscillatory and patterning dynamics in Notch signalling, allowing for the control of the tempo and outcome of inter-cellular Notch signalling.
