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

Area of Science:

• Developmental biology
• Systems biology
• Theoretical biology

Background:

• The Delta-Notch-Hes signaling pathway regulates diverse developmental processes, including somite formation and tissue patterning.
• Its broad patterning capabilities stem from the tunable dynamics of the Notch-Hes feedback circuit, exhibiting pulsatile and switching behaviors.
• Understanding how lateral inhibition between cells with monostable, oscillatory, or bistable dynamics generates spatiotemporal patterns is a key theoretical challenge.

Purpose of the Study:

• To investigate the spatiotemporal pattern formation arising from lateral inhibition in a model of the Delta-Notch-Hes pathway.
• To determine how intracellular and intercellular parameters influence the stability and diversity of these patterns.
• To explore the theoretical basis for robust and defect-free spatial pattern generation during development.

Main Methods:

• A discrete cell lattice model was employed, with intracellular dynamics represented by a phase-like variable.
• The model incorporates a cross-shaped phase diagram to describe cellular states.
• Analysis focused on the dependence of spatially inhomogeneous and temporally synchronized states on model parameters.

Main Results:

• The study reveals parameter-dependent multistability, where diverse spatiotemporal patterns coexist.
• These patterns exhibit tunable and robust transition scenarios crucial for defect-free spatial patterning.
• The findings are consistent with regulatory network modeling of the Delta-Notch-Hes pathway.

Conclusions:

• The Delta-Notch-Hes pathway's broad spatiotemporal patterning capabilities arise from multistability within its feedback circuit.
• Tunable intracellular and intercellular parameters allow for robust generation of complex developmental patterns.
• This theoretical framework supports the understanding of how biological systems achieve precise spatial organization.