Intercellular signaling drives robust cell fate and patterning in multicellular systems

Cells do not act in isolation; they communicate with each other through a complex network of signals. In multicellular organisms, cell signaling buffers against fluctuations in gene expression. Its effect, however, on multistability—the ability of genetically identical cells to take on and maintain diverse stable states or phenotypes—is unclear. We develop spatially explicit stochastic models that couple fine-grained gene regulatory dynamics with intercellular signaling to study cell fate control in multicellular tissues. We show that intercellular signaling acts as a switch-like controller of cell fate, driving transitions from transient to stable states across tissues. Even weak signaling stabilizes short-lived expression states, and we derive mathematical expressions for the threshold signaling strength required to trigger tissue-wide stabilization. We also derive a universal spatial limit: stable region size grows only sublinearly with signaling strength, implying that large stable regions are prohibitively costly to maintain. The resulting trade-off between robustness and signaling in cell fate control highlights the delicate balance required during developmental processes to maintain spatial precision and provides insight into how organisms regulate tissue structure.