Oscillatory Notch pathway activity in a delay model of neuronal differentiation

Abstract

Lateral inhibition resulting from a double-negative feedback loop underlies the assignment of different fates to cells in many developmental processes. Previous studies have shown that the presence of time delays in models of lateral inhibition can result in significant oscillatory transients before patterned steady states are reached. We study the impact of local feedback loops in a model of lateral inhibition based on the Notch signalling pathway, elucidating the roles of intracellular and intercellular delays in controlling the overall system behaviour. The model exhibits both in-phase and out-of-phase oscillatory modes, and oscillation death. Interactions between oscillatory modes can generate complex behaviours such as intermittent oscillations. Our results provide a framework for exploring the recent observation of transient Notch pathway oscillations during fate assignment in vertebrate neurogenesis.

17 figures, to appear in Phys Rev E

References in corpus (2)

• Time Delay Induced Death in Coupled Limit Cycle Oscillators
• Delayed coupling theory of vertebrate segmentation

Cited by in corpus (8)

• Intercellular Coupling Regulates the Period of the Segmentation Clock
• The Role of the Hes1 Crosstalk Hub in Notch-Wnt Interactions of the Intestinal Crypt
• Collective modes of coupled phase oscillators with delayed coupling
• Modeling delayed processes in biological systems
• General model of a cascade of reactions with time delays: global stability analysis
• Intrinsic noise, Delta-Notch signalling and delayed reactions promote sustained, coherent, synchronised oscillations in the presomitic mesoderm
• Embryonic lateral inhibition as optical modes: an analytical framework for mesoscopic pattern formation
• Modelling Population-Level Hes1 Dynamics: Insights from a Multi-Framework Approach