Synthetic reaction-diffusion patterning in mammalian cells
- 1Caltech, Howard Hughes Medical institute
Abstract
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.
Related
- A step toward synthetic endosymbiosis: introducing Escherichia coli and the trypanosomatid endosymbiont Candidatus Kinetoplastibacterium crithidii into mammalian cells using a polyethylene glycol-based fusion protocol
- Temperature scaling of developmental tempo reveals reaction-dominated morphogen patterning
- Proteolytic dissection of eIF4G reveals that closed-loop mRNP formation is dispensable for bulk translation in mammalian cells
- Universal donor plasmids for biallelic degron-tagging in mammalian cells and organoids
- Fluorescence Correlation Spectroscopy To Study Diffusion and Reaction of Bacteriophages inside Biofilms
BibTeX
@misc{wang2026synthetic,
title = {{Synthetic reaction-diffusion patterning in mammalian cells}},
author = {S. Wang and R. Du and J. M. Linton and M. B. Elowitz},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.763437},
url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763437v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Synthetic reaction-diffusion patterning in mammalian cells
AU - S. Wang
AU - R. Du
AU - J. M. Linton
AU - M. B. Elowitz
PY - 2026
DA - 2026/11/01
PB - bioRxiv
DO - 10.64898/2026.11.01.763437
UR - https://www.biorxiv.org/content/10.64898/2026.11.01.763437v1
AB - 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.
ER -