Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves

Ahmet Ay, Jack Holland, Adriana Sperlea, Gnanapackiam Sheela Devakanmalai, Stephan Knierer, Sebastian Sangervasi, Angel Stevenson, Ertugğrul M. Özbudak

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in travelingwaves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations have been proposed, the mechanism underlying traveling waves has remained elusive. Here, we combined molecularlevel computationalmodeling and quantitative experimentation to solve this puzzle.Ourmodelpredictsthe existenceofan increasinggradientof gene expression time delays along the posterior to anterior direction to recapitulate spatiotemporal profiles of the traveling segmentation clock waves in different genetic backgrounds in zebrafish. We validated this prediction by measuring an increased time delay of oscillatory Her1 protein production along the unsegmented tissue. Our results refuted the need for spatial expansion of the core feedback loop to explain the occurrence of traveling waves. Spatial regulation of gene expression time delays is a novel way of creating dynamic patterns; this is the first report demonstrating such a controlmechanismin any tissue and future investigations will explore the presence of analogous examples in other biological systems.

Original languageEnglish (US)
Pages (from-to)4158-4167
Number of pages10
JournalDevelopment (Cambridge)
Issue number21
StatePublished - Nov 1 2014
Externally publishedYes


  • Computational modeling
  • Gene expression
  • Oscillation
  • Segmentation clock
  • Systems biology
  • Traveling wave

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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