A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest
Fig 5
Mathematical modelling and refinement of the preliminary iridophore GRN.
Graphical representation, simulation outputs and PCA of Monte Carlo results for models A1 (A,D,G), A2 (B,E,H) and A3 (C,F,I)). In the schematics (A-C), green rectangular nodes are used for transcription factor-coding genes, blue rectangles for transmembrane receptors and red circles for enzymes. Transcriptional activation is indicated by red arrows. Solid edges represent known direct interactions, whereas dashed lines indicate known indirect or interactions where their nature is unknown. These diagrams are mathematically described using ODEs, the numerical solutions of which indicate how the gene expression dynamics progress in WT and mutant scenarios (D-F). In the simulation outputs (D-F), lines and arrowheads (where lines are overlapping), coloured according to the key in (D), indicate the change of concentration (nM) for each gene output during the course of iridophore development (hpf). The simulation considers the developing iridophore lineage starting from tfec+;sox10+;ltk-;mitfa-;pnp4a- NCCs of the ARPT at 18 hpf. Qualitative assessment of simulation outputs is indicated as follows for each gene. Green tick: modelling predictions match experimental observations. Crosses: prediction for a specific gene (indicated by colour of the cross, matching gene reference colour as indicated in the legend) is refuted by experimental evidence. (G-I) PCA plots for models A1-A3. Axes plot principal components (PC) 1, 2 and 3. All trials using model A1 fail the set criteria, thus scoring between 0–0.2 (G, turquoise spots). Under model A2, a small proportion of parameter sets scores within the range of 25–55 (H, dark blue and purple spots) and no trials score above S = 55 (magenta spots). Under model A3, performance improves notably, with more trials scoring between 25 and 55 (I, dark blue and purple spots), but still no trials score above S = 55 (magenta spots).