Noise-resistant developmental reproducibility in vertebrate somite formation

Area of Science:

• Developmental biology
• Computational biology
• Systems biology

Background:

• Embryonic development exhibits remarkable reproducibility despite single-cell molecular noise.
• Understanding how multicellular systems achieve robustness against stochasticity is crucial.
• Vertebrate somitogenesis serves as a model for studying developmental reproducibility.

Purpose of the Study:

• Investigate the effect of intrinsic noise on developmental reproducibility in somitogenesis.
• Elucidate the role of the segmentation clock in maintaining somite formation regularity.
• Develop a computational model to simulate ERK-mediated somitogenesis and noise effects.

Main Methods:

• Developed a computational model of ERK-mediated somitogenesis incorporating FGF gradient, cell-cell communication, and segmentation clock.
• Simulated model behavior under varying noise levels.
• Performed theoretical analysis to understand the clock's role in noise resistance.

Main Results:

• Model simulations reproduced observed step-like ERK activity gradients and stepwise clock-driven boundary shifts.
• Somite regularity was robustly maintained against noise in the model.
• Removing the clock led to irregular ERK activity shifts and somite size variation, consistent with experimental data.

Conclusions:

• The segmentation clock plays a novel role in noise-resistant developmental reproducibility.
• The clock mechanism actively reduces somite irregularity caused by intrinsic noise.
• This study provides insights into how biological systems achieve robust pattern formation.