# Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans

## TL;DR

This paper identifies a gene network in C. elegans epidermal stem cells and shows how CEH-16 represses egl-18 during development.

## Contribution

A novel quantitative gene network for C. elegans seam cells inferred using mathematical modeling and experimental validation.

## Key findings

- CEH-16 represses egl-18 across early larval stages in C. elegans seam cells.
- Mathematical modeling validates the regulatory interaction between CEH-16 and egl-18.
- The model accurately predicts mRNA levels after perturbing ceh-16 and egl-18.

## Abstract

Gene regulatory networks are crucial in cellular decision-making, making the inference of their architecture essential for understanding organismal development. The gene network of Caenorhabditis elegans epidermal stem cells, known as seam cells, remains undefined. Here, we integrate experimental data, mathematical modeling, and statistical inference to investigate this network, focusing on three core transcription factors (TFs), namely ELT-1, EGL-18, and CEH-16. We use single-molecule FISH to quantify TF mRNA levels in single seam cells of wild-type and mutant backgrounds across four early larval stages. Using Modular Response Analysis, we predict TF interactions and uncover a repressive interaction between CEH-16 and egl-18 consistent across time points. We validate its significance at the L1 stage with ordinary differential equations and Bayesian modeling, making testable predictions for a double mutant. Our findings reveal TF regulatory relationships in seam cells and demonstrate a flexible mathematical framework for inferring gene regulatory networks from gene expression data.

•We construct a quantitative gene network for seam cells from gene expression data•We find that CEH-16 represses egl-18 throughout early larval stages•Mathematical modeling and inference validate the importance of this interaction•Our model accurately predicts mRNA levels upon the perturbation of ceh-16 and egl-18

We construct a quantitative gene network for seam cells from gene expression data

We find that CEH-16 represses egl-18 throughout early larval stages

Mathematical modeling and inference validate the importance of this interaction

Our model accurately predicts mRNA levels upon the perturbation of ceh-16 and egl-18

Bioinformatics; Biological sciences; Cell biology; Gene network