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Modelling asymmetric somitogenesis: Deciphering the mechanisms behind species differences.

Renske M A Vroomans1, Kirsten H W J Ten Tusscher1

  • 1Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.

Developmental Biology
|May 17, 2017
PubMed
Summary

Retinoic acid (RA) inhibition disrupts vertebrate bilateral symmetry, causing asymmetric somitogenesis. Species-specific differences in FGF signaling and somite determination mechanisms explain variations in left-right asymmetry, as revealed by computational modeling.

Keywords:
Computational modellingDetermination frontLeft-right signallingPresomitic mesodermSegmentation clockSomitogenesis

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Area of Science:

  • Developmental biology
  • Comparative genomics
  • Computational modeling

Background:

  • Somitogenesis establishes vertebrate bilateral symmetry.
  • Retinoic acid (RA) inhibition disrupts this symmetry, influencing left-right determination.
  • Species-specific differences exist in somitogenesis gene oscillations and patterning.

Purpose of the Study:

  • To decipher the causes of species differences in asymmetric somitogenesis using computational modeling.
  • To investigate the roles of FGF asymmetry and somite determination dynamics.
  • To understand how variations in these mechanisms lead to distinct left-right asymmetric phenotypes.

Main Methods:

  • Computational modeling of the clock-and-wavefront mechanism.
  • Incorporation of species-specific data on FGF gradients and somitogenesis frequency.
  • Extension of basic models to include species-specific determination mechanisms.

Main Results:

  • A simple clock-and-wavefront model reproduced chicken asymmetric somitogenesis.
  • FGF signaling asymmetry alone did not fully explain mouse or zebrafish phenotypes.
  • Extended models incorporating species-specific determination dynamics were necessary to reproduce mouse and zebrafish asymmetry.

Conclusions:

  • Species differences in asymmetric somitogenesis arise from a combination of FGF dynamics and somite determination mechanisms.
  • Computational models are powerful tools for understanding somitogenesis and left-right asymmetry.
  • Studying left-right asymmetry provides deeper insights into the fundamental processes of somitogenesis.