5 research outputs found
How Criticality of Gene Regulatory Networks Affects the Resulting Morphogenesis under Genetic Perturbations
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.Comment: 34 pages, 17 figures, 1 tabl
The Role of Criticality of Gene Regulatory Networks on Emergent Properties of Biological Systems
The relationship between criticality of gene regulatory networks (GRNs) and dynamics of GRNs at a single cell level has been vigorously studied. However, the relationship between the criticality of GRNs and properties of multicellular organisms at a higher level has not been fully explored. Here we aim at revealing potential roles of the criticality of GRNs at a multicellular and hierarchical level, using a random Boolean network as a GRN. We perform three studies. Firstly, we propose a GRN-based morphogenetic model, and delve into the role of the criticality of GRNs in morphogenesis at a multicellular level. Secondly, we include an evolutionary context in our morphogenetic model by introducing genetic perturbations (e.g., mutations) to GRNs, and examine whether the role of the criticality of GRNs can be maintained even in the presence of the evolutionary perturbations. Also, we look into what the resulting morphologies are like and what kind of biological implications they have from the epigenetic viewpoint in morphology. Lastly, we present multilayer GRNs consisting of an intercellular layer and an intracellular layer. A network in an intercellular layer represents interactions between cells, and a network in an intracellular layer means interactions between genes. All the nodes of an intercellular network have identical intracellular GRNs. We investigate how the criticality of GRNs affects the robustness and evolvability of the multilayer GRNs at a hierarchical level, depending on cellular topologies and the number of links of an intercellular network. From the three studies, we found that the criticality of GRNs facilitated the formation of nontrivial morphologies at a multicellular level, and generated robust and evolvable multilayer GRNs most frequently at a hierarchical level. Our findings indicate that the roles of the criticality of GRNs are hard to be discovered through the single-cell-level studies. It justifies the value of our research on the relationship between criticality of GRNs and properties of organisms in the context of multicellular settings