Synthetic reaction-diffusion patterning in mammalian cells

During development, periodic patterns arise through reaction-diffusion (RD) circuits involving local activation and long-range inhibition (LALI). Natural systems are complex, typically entangling regulation and transport in the same morphogens. It remains unclear what minimal circuits are sufficient for LALI patterning in mammalian cells, and whether they can be implemented in a modular fashion, allowing independent control of regulation and transport. Here, we designed synthetic LALI circuits using three natural and synthetic signaling systems, BMP, Activin, and the SNIPR pathway, and showed that they generate spatial patterns with distinct characteristic spatial scales. Model-guided design allowed flexible morphogen reassignment, with BMP4 acting as either short-range activator or long-range inhibitor. Gene expression noise degraded long-range order but preserved the dominant local spatial scale. Together, these results provide a modular, extensible synthetic framework for engineered patterning in mammalian cells.