How Criticality of Gene Regulatory Networks Affects the Resulting Morphogenesis under Genetic Perturbations

TL;DR

This study explores how the criticality of gene regulatory networks influences multicellular morphogenesis, revealing that criticality promotes complex pattern formation and tissue organization under genetic perturbations.

Contribution

It uncovers the role of GRN criticality at a multicellular level, linking network properties to morphogenetic pattern formation and tissue structure.

Findings

Critical GRNs facilitate nontrivial morphologies.

Criticality leads to homogeneous cell clusters.

Structured tissues may originate from GRN criticality.

Abstract

Whereas the relationship between criticality of gene regulatory networks (GRNs) and dynamics of GRNs at a single cell level has been vigorously studied, the relationship between the criticality of GRNs and system properties at a higher level has remained unexplored. Here we aim at revealing a potential role of criticality of GRNs at a multicellular level which are hard to uncover through the single-cell-level studies, especially from an evolutionary viewpoint. Our model simulated the growth of a cell population from a single seed cell. All the cells were assumed to have identical GRNs. We induced genetic perturbations to the GRN of the seed cell by adding, deleting, or switching a regulatory link between a pair of genes. From numerical simulations, we found that the criticality of GRNs facilitated the formation of nontrivial morphologies when the GRNs were critical in the presence of the evolutionary perturbations. Moreover, the criticality of GRNs produced topologically homogenous cell clusters by adjusting the spatial arrangements of cells, which led to the formation of nontrivial morphogenetic patterns. Our findings corresponded to an epigenetic viewpoint that heterogeneous and complex features emerge from homogeneous and less complex components through the interactions among them. Thus, our results imply that highly structured tissues or organs in morphogenesis of multicellular organisms might stem from the criticality of GRNs.