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Related Experiment Videos

Modeling the Hes1 oscillator.

Stefan Zeiser1, Johannes Müller, Volkmar Liebscher

  • 1GSF-National Research Centre for Environment and Health, Institute of Biomathematics and Biometry, Oberschleissheim, Germany. zeiser@gsf.de

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
|September 7, 2007
PubMed
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Somitogenesis, the segmentation of vertebrate embryos, may be driven by ultradian clocks like the Hes1 gene. This study estimates the Hes1 gene

Area of Science:

  • Developmental Biology
  • Systems Biology
  • Molecular Biology

Background:

  • Somitogenesis, the formation of embryonic segments (somites), is regulated by biological clocks.
  • Ultradian clocks, with short cycle times, are hypothesized to drive somitogenesis.
  • The bHLH factor Hes1, through negative autoregulation, is a candidate molecular clock for this process.

Purpose of the Study:

  • To estimate the Hill coefficient for the Hes1 gene's transcriptional switch.
  • To propose a more detailed model of the Hes1 autoregulative network.
  • To investigate the role of synergistic binding in Hes1 regulation.

Main Methods:

  • Analysis of Hes1 gene promoter binding sites.
  • Modeling the Hes1 negative feedback loop using a Goodwin system.

Related Experiment Videos

  • Mathematical modeling with delay equations and Hill functions.
  • Varying the number of linear differential equations to determine oscillation parameters.

    • Main Results:

    • Evidence suggests limited synergistic binding at the Hes1 promoter.
    • The estimated Hill coefficient for Hes1 regulation is approximately three.
    • Sustained oscillations are observed in models with a sufficient number of differential equations.
    • A rational lower bound for the Hill coefficient was determined.

    Conclusions:

    • The Hes1 oscillator's Hill coefficient is likely around three, indicating specific regulatory dynamics.
    • The findings suggest that nonlinear processes beyond the Hes1 regulatory region contribute to the oscillator's function.
    • This research refines models of molecular clocks involved in embryonic development.