Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

Development. 2021 Feb 25;148(4):dev197566. doi: 10.1242/dev.197566.

Abstract

During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.

Keywords: Dynamical systems theory; Gene regulatory network; Morphogen signaling; Neural tube; cis regulatory elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Body Patterning / genetics*
  • Embryonic Development
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Mice
  • PAX6 Transcription Factor / genetics
  • PAX6 Transcription Factor / metabolism
  • Regulatory Sequences, Ribonucleic Acid

Substances

  • Biomarkers
  • PAX6 Transcription Factor
  • Pax6 protein, mouse
  • Regulatory Sequences, Ribonucleic Acid