A Feedback Quenched Oscillator Produces Turing Patterning with One Diffuser

Efforts to engineer synthetic gene networks that spontaneously produce patterning in multicellular ensembles have focused on Turing's original model and the “activator-inhibitor” models of Meinhardt and Gierer. Systems based on this model are notoriously difficult to engineer. We present the first demonstration that Turing pattern formation can arise in a new family of oscillator-driven gene network topologies, specifically when a second feedback loop is introduced which quenches oscillations and incorporates a diffusible molecule. We provide an analysis of the system that predicts the range of kinetic parameters over which patterning should emerge and demonstrate the system's viability using stochastic simulations of a field of cells using realistic parameters. The primary goal of this paper is to provide a circuit architecture which can be implemented with relative ease by practitioners and which could serve as a model system for pattern generation in synthetic multicellular systems. Given the wide range of oscillatory circuits in natural systems, our system supports the tantalizing possibility that Turing pattern formation in natural multicellular systems can arise from oscillator-driven mechanisms. Author Summary: The production of patterns in gene expression in an ensemble of cells is a phenomenon central to the development of multi-cellular organisms. Here we provide an exciting new result regarding diffusion-driven instability, a mechanism for spontaneous pattern formation originally proposed by Alan Turing. Efforts along this front have focused almost exclusively on Turing's original model and the “activator-inhibitor” models of Meinhardt and Gierer, but have yet to yield an experimental demonstration of a robust, tunable system that can break symmetry and spontaneously generate gene expression patterns. In this paper we propose a new family of oscillator-driven gene network topologies capable of Turing pattern formation. We believe this would be of significant impact to both emerging efforts at engineering multicellularity in the synthetic biology community as well as new guidance for those groups looking for similar phenomena in natural systems. Given the wide range of oscillatory circuits in natural systems, our system supports the tantalizing possibility that Turing pattern formation in natural multicellular systems can arise from oscillator-driven mechanisms. We provide an analysis of the system that predicts the range of parameters over which patterning should emerge and demonstrate the system's viability using stochastic simulations of a field of cells using realistic parameters.