Short-lived her proteins drive robust synchronized oscillations in the Zebrafish segmentation clock

Ahmet Ay, Stephan Knierer, Adriana Sperlea, Jack Holland, Ertuǧrul M. Özbudak

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Oscillations are prevalent in natural systems. A gene expression oscillator, called the segmentation clock, controls segmentation of precursors of the vertebral column. Genes belonging to the Hes/her family encode the only conserved oscillating genes in all analyzed vertebrate species. Hes/Her proteins form dimers and negatively autoregulate their own transcription. Here, we developed a stochastic two-dimensional multicellular computational model to elucidate how the dynamics, i.e. period, amplitude and synchronization, of the segmentation clock are regulated. We performed parameter searches to demonstrate that autoregulatory negative-feedback loops of the redundant repressor Her dimers can generate synchronized gene expression oscillations in wild-type embryos and reproduce the dynamics of the segmentation oscillator in different mutant conditions. Our model also predicts that synchronized oscillations can be robustly generated as long as the half-lives of the repressor dimers are shorter than 6 minutes. We validated this prediction by measuring, for the first time, the half-life of Her7 protein as 3.5 minutes. These results demonstrate the importance of building biologically realistic stochastic models to test biological models more stringently and make predictions for future experimental studies.

Original languageEnglish (US)
Pages (from-to)3244-3253
Number of pages10
JournalDevelopment (Cambridge)
Volume140
Issue number15
DOIs
StatePublished - Aug 1 2013

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Zebrafish
Gene Expression
Biological Models
Genes
Half-Life
Vertebrates
Proteins
Spine
Embryonic Structures

Keywords

  • Computational modeling
  • Oscillation
  • Protein half-life
  • Segmentation clock
  • Systems biology
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Short-lived her proteins drive robust synchronized oscillations in the Zebrafish segmentation clock. / Ay, Ahmet; Knierer, Stephan; Sperlea, Adriana; Holland, Jack; Özbudak, Ertuǧrul M.

In: Development (Cambridge), Vol. 140, No. 15, 01.08.2013, p. 3244-3253.

Research output: Contribution to journalArticle

Ay, Ahmet ; Knierer, Stephan ; Sperlea, Adriana ; Holland, Jack ; Özbudak, Ertuǧrul M. / Short-lived her proteins drive robust synchronized oscillations in the Zebrafish segmentation clock. In: Development (Cambridge). 2013 ; Vol. 140, No. 15. pp. 3244-3253.
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