Quantitative Modelling of Diffusion-driven Pattern Formation in microRNA-regulated Gene Expression

TL;DR

This paper develops mathematical models to understand how microRNA regulation can generate spatial and temporal patterns in gene expression, shedding light on developmental processes and cell fate decisions.

Contribution

It introduces detailed dynamical and reaction-diffusion models for microRNA-mediated gene regulation, revealing mechanisms of pattern formation and cell fate determination.

Findings

MicroRNA regulation can produce persistent spatial-temporal patterns.

Competitive microRNA effects can influence developmental patterning.

Coordinated regulation can induce patterns from homogeneous conditions.

Abstract

MicroRNAs are extensively known for post-transcriptional gene regulation and pattern formation in the embryonic developmental stage. We explore the origin of these spatio-temporal patterns mathematically, considering three different motifs here. For three scenarios, (1) simple microRNA-based mRNA regulation with a graded response in output, (2) microRNA-based mRNA regulation resulting in bistability in the dynamics, and (3) a coordinated response of microRNA (miRNA), simultaneously regulating the mRNAs of two different pools, detailed dynamical analysis, as well as the reaction-diffusion scenario have been considered and analyzed in the steady state and for the transient dynamics further. We have observed persistent-temporal patterns, as a result of the dynamics of the motifs, that explain spatial gradients and relevant patterns formed by related proteins in development and phenotypic heterogenetic aspects in biological systems. Competitive effects of miRNA regulation have also been found to be capable to cause spatio-temporal patterns, persistent enough to direct developmental decisions. Under coordinated regulation, miRNAs are found to generate spatio-temporal patterning even from complete homogeneity in concentration of target protein, which may have impactful insights in choice of cell-fates.