Temporal variability and cell mechanics control robustness in mammalian embryogenesis

Area of Science:

• Developmental biology
• Cellular dynamics
• Biophysics

Background:

• Living systems exhibit remarkable precision in form and function despite inherent randomness (stochasticity).
• Understanding how biological systems achieve robustness against noise is a key challenge.

Purpose of the Study:

• To investigate the mechanisms underlying robust patterning in early embryogenesis.
• To determine the role of cell division timing and cellular topology in achieving precise embryonic form.

Main Methods:

• Generation of morphomaps for preimplantation embryos (mouse, rabbit, monkey).
• Application of topological analysis and genetic perturbations.
• Development of a physical model incorporating actomyosin contractility and noise.

Main Results:

• 8-cell embryos converged to robust 3D shapes despite desynchronized divisions.
• Embryos transitioned to preferred cellular topologies, predictable by a physical model.
• Actomyosin contractility and noise facilitated topological transitions, reducing surface energy.
• Stochastic division timing promoted regular embryo packing and increased inner cell numbers.

Conclusions:

• Stochasticity in cell division timing is crucial for robust embryonic patterning.
• A physical model explains how cellular contractility and noise drive topological changes.
• This mechanism ensures regular embryo packing and optimal cell allocation for development.