RRC ID 76934
Author Tokuoka M, Satou Y.
Title A digital twin reproducing gene regulatory network dynamics of early Ciona embryos indicates robust buffers in the network.
Journal PLoS Genet
Abstract How gene regulatory networks (GRNs) encode gene expression dynamics and how GRNs evolve are not well understood, although these problems have been studied extensively. We created a digital twin that accurately reproduces expression dynamics of 13 genes that initiate expression in 32-cell ascidian embryos. We first showed that gene expression patterns can be manipulated according to predictions by this digital model. Next, to simulate GRN rewiring, we changed regulatory functions that represented their regulatory mechanisms in the digital twin, and found that in 55 of 100 cases, removal of a single regulator from a conjunctive clause of Boolean functions did not theoretically alter qualitative expression patterns of these genes. In other words, we found that more than half the regulators gave theoretically redundant temporal or spatial information to target genes. We experimentally substantiated that the expression pattern of Nodal was maintained without one of these factors, Zfpm, by changing the upstream regulatory sequence of Nodal. Such robust buffers of regulatory mechanisms may provide a basis of enabling developmental system drift, or rewiring of GRNs without changing expression patterns of downstream genes, during evolution.
Volume 19(9)
Pages e1010953
Published 2023-9-1
DOI 10.1371/journal.pgen.1010953
PMID 37756274
PMC PMC10530022
MeSH Animals Ciona* Ciona intestinalis* / genetics Gene Regulatory Networks / genetics Transforming Growth Factor beta
IF 5.175
C.intestinalis / (O.japonicus) Wild C. int