Oscillatory Notch pathway activity in a delay model of neuronal differentiation

TL;DR

This paper models how delays in Notch signaling influence oscillations during neuronal differentiation, revealing complex behaviors like oscillation death and intermittent oscillations relevant to vertebrate neurogenesis.

Contribution

It introduces a delay-based model of Notch pathway activity that explains oscillatory behaviors observed during neuronal fate decisions.

Findings

Model exhibits in-phase and out-of-phase oscillations

Delays induce oscillation death and complex transient behaviors

Provides framework for understanding Notch oscillations in neurogenesis

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.