Mechanochemical bistability as a principle of robust morphogenesis

Area of Science:

• Developmental Biology
• Biophysics
• Cell Biology

Background:

• Embryogenesis involves physical forces and biochemical signals, but their coordination for reproducible morphogenesis is unclear.
• The developing vertebrate intestine serves as a model to study these complex developmental processes.

Purpose of the Study:

• To investigate how physical forces and biochemical signals coordinate during intestinal crypt budding.
• To understand the mechanisms ensuring robust and reproducible morphogenesis in developing organs.

Main Methods:

• Organoid systems
• Biophysical modeling
• Pharmacological perturbations
• In vivo studies of the developing vertebrate intestine

Main Results:

• Mechanochemical bistability, driven by actomyosin tension and luminal pressure feedback, ensures robust and irreversible crypt budding.
• This bistability provides tight control over crypt morphology during development and insensitivity to fluctuations post-completion.
• In vivo, enterocyte swelling activates a cPLA₂-dependent pathway, synchronizing stem cell contractility and preventing divergence.

Conclusions:

• A multi-tiered strategy coordinates global tissue mechanics with local mechanosensation to buffer variability and ensure convergent morphogenesis.
• Mechanochemical bistability and tissue-level mechanical coordination may be general principles for robust patterning in developmental and organoid systems.