Multistability and transitions between spatiotemporal patterns through versatile Notch-Hes signaling

Abstract

The Delta-Notch-Hes signaling pathway is involved in various developmental processes ranging from the formation of somites to the dynamic fine-grained patterns of cell types in developing or regenerating tissues. Such broad patterning capabilities rely in part on the versatile and tunable dynamics of the Notch-Hes feedback circuit eliciting both pulsatile and switching behaviors. This raises the theoretical issue of which specific spatiotemporal features emerge from lateral inhibition between cells that can display and transit between monostable, oscillatory and bistable regimes. To address this issue, I consider a discrete cell lattice model where intracellular dynamics is described by a phase-like variable and displays a typical cross-shaped phase diagram. Model analysis determines how the existence and stability of many spatially inhomogeneous and temporally synchronized states depends on key intracellular and intercellular parameters. It reveals a parameter-dependent multistability between those diverse spatiotemporal patterns, giving rise to tunable and robust developmental transition scenarios ensuring defect-free spatial patterns. Such broad repertoire and multistability of spatiotemporal patterns is corroborated with regulatory network modeling of the Delta-Notch-Hes pathway.