# Controllability of the gene regulatory network in zebrafish embryogenesis

## TL;DR

This study explores how gene regulatory networks in zebrafish embryos change and become more controllable as development progresses.

## Contribution

The study introduces a novel approach to analyze controllability of gene regulatory networks across developmental stages in zebrafish.

## Key findings

- About 80% of nodes in inferred gene regulatory networks are driver nodes in most developmental stages.
- The fraction of driver nodes decreases in the final developmental phase, indicating increased controllability.
- Critical transcription factors were identified as potential key regulatory points in the network.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-025-33869-9.