Controllability of the gene regulatory network in zebrafish embryogenesis.

The development in multicellular organisms is governed by gene regulatory networks (GRNs), which are often difficult to control by the theory of network controllability. While transcription factors (TFs) have been studied, the controllability of the entire developmental process, from early embryo to terminal differentiation, remains unclear. To address this, we reconstructed inferred GRNs across developmental stages using single-cell RNA sequencing data from zebrafish embryogenesis. We inferred networks for both trunk and branch trajectories, and calculated the fraction of driver nodes for each. About 80% of nodes were driver nodes in most networks. Notably, the fraction of driver nodes was significantly lower at the final developmental phase than in earlier phases, suggesting that inferred GRNs become more controllable as development progresses. Furthermore, we identified critical TFs-defined as transcription factors originating from critical edges-that may highlight key regulatory points.