Study and Modeling of Biological Noise-Filtering Properties of Conserved Gene Regulatory Networks Motifs in Animal Development

Abstract

ABSTRACTBiological noise results from heterogeneous gene expression levels among a group of cells [1]. This heterogeneity is due to the variation in gene expression that occurs over time at the single-cell level. Some noise-filtering mechanisms like redundancy in genetic circuits have been identified. Likewise, the feed-forward loop network motif has been found to have noise-filtering capacities in animal development. On the other hand, previous studies have contradictory conclusions about the noise-filtering capacities of the feedback loop and none of them have studied this capacity in the activator-inhibitor regulatory system. Here we studied some dynamical properties, such as noise and expression levels, in self-activated and activator-inhibitor regulatory systems, both at the unicellular and multicellular levels. These systems are essential in the self-patterning and community effect processes occurring in development and differentiation. We used the three-stage model to represent the expression of a gene with promoter regulation and Hill functions to represent the regulatory connections between genes. We used Gillespie’s Algorithm and the Chemical Langevin Equation for simulations. The regulatory systems evaluated do not reduce the biological noise. On the contrary, the noise remains at the same level or increases in comparison with an unregulated gene. The noise levels in these systems depend on the gene expression type of both the regulator and the regulated gene. In this way, the particular forms in which genes connect to each other in these regulatory systems do not explain the noise in expression. However, the noise has a propagation pattern different for activation and inactivation types of regulation. Finally, the diffusion and colony size could be mechanisms of noise filtering in gene expression in a colony of cells. The increase in diffusion rate and colony size are necessary to synchronize gene expression and perform the community effect in embryonic development.