Response to Nodal morphogen gradient is determined by the kinetics of target gene induction

Elife. 2015 Apr 14:4:e05042. doi: 10.7554/eLife.05042.

Abstract

Morphogen gradients expose cells to different signal concentrations and induce target genes with different ranges of expression. To determine how the Nodal morphogen gradient induces distinct gene expression patterns during zebrafish embryogenesis, we measured the activation dynamics of the signal transducer Smad2 and the expression kinetics of long- and short-range target genes. We found that threshold models based on ligand concentration are insufficient to predict the response of target genes. Instead, morphogen interpretation is shaped by the kinetics of target gene induction: the higher the rate of transcription and the earlier the onset of induction, the greater the spatial range of expression. Thus, the timing and magnitude of target gene expression can be used to modulate the range of expression and diversify the response to morphogen gradients.

Keywords: DNA binding affinity; developmental biology; morphogen gradient; signal transduction; stem cells; transcription rate; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Patterning / drug effects
  • Body Patterning / genetics
  • Endoderm / drug effects
  • Endoderm / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Green Fluorescent Proteins / metabolism
  • Kinetics
  • Mice
  • Models, Biological
  • Nodal Protein / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Smad2 Protein / metabolism
  • Time Factors
  • Transcription, Genetic / drug effects
  • Transcriptional Activation*
  • Transgenes
  • Zebrafish / embryology
  • Zebrafish / genetics

Substances

  • Nodal Protein
  • Smad2 Protein
  • Green Fluorescent Proteins