Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks

During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify the properties of a network that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise to increase patterning precision. These results establish design principles of gene regulatory networks that produce precise patterns of gene expression.