Precision in a rush: Trade-offs between reproducibility and steepness of the hunchback expression pattern

PLoS Comput Biol. 2018 Oct 11;14(10):e1006513. doi: 10.1371/journal.pcbi.1006513. eCollection 2018 Oct.

Abstract

Fly development amazes us by the precision and reproducibility of gene expression, especially since the initial expression patterns are established during very short nuclear cycles. Recent live imaging of hunchback promoter dynamics shows a stable steep binary expression pattern established within the three minute interphase of nuclear cycle 11. Considering expression models of different complexity, we explore the trade-off between the ability of a regulatory system to produce a steep boundary and minimize expression variability between different nuclei. We show how a limited readout time imposed by short developmental cycles affects the gene's ability to read positional information along the embryo's anterior posterior axis and express reliably. Comparing our theoretical results to real-time monitoring of the hunchback transcription dynamics in live flies, we discuss possible regulatory strategies, suggesting an important role for additional binding sites, gradients or non-equilibrium binding and modified transcription factor search strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / growth & development
  • Gene Expression Regulation, Developmental / genetics*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Larva
  • Models, Genetic*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Trans-Activators
  • Transcription Factors
  • bcd protein, Drosophila
  • hb protein, Drosophila

Grants and funding

This work was supported by Paris Sciences Lettres (PSL) IDEX REFLEX (ND, AMW, MC), Foundation ARC pour la Recherche sur le Cancer ARC PJA20151203341 (ND), L’Agence nationale de la recherche (ANR)-11-LABX-0044 DEEP Labex (ND) and PSL ANR-10-IDEX-0001-02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. https://www.psl.eu/enhttps://www.fondation-arc.org/http://www.agence-nationale-recherche.fr/.