Robustness under functional constraint: The genetic network for temporal expression in Drosophila neurogenesis

TL;DR

This study investigates the gene regulatory network controlling sequential gene expression in Drosophila neurogenesis, revealing a robust regulatory module that ensures precise timing despite biological variability.

Contribution

It identifies a specific regulatory module responsible for robust sequential gene expression and demonstrates its stability under various perturbations in Drosophila neurogenesis.

Findings

The identified network is highly robust against parameter variations.

A regulatory module of three types of regulations underpins precise gene sequencing.

Predicted unknown regulatory factors match experimental gene expression profiles.

Abstract

Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts sequentially express a group of genes in a definite order, which generates the diversity of cell types. By producing all possible regulatory networks of these genes and examining their expression dynamics numerically, we identify requisite regulations and predict an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. We then evaluate the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three kinds of regulations which is responsible for precise sequential expression. The present study suggests an underlying principle on how biological systems are robustly designed under functional constraint.