A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation

Area of Science:

• Developmental Biology
• Biophysics
• Computational Biology

Background:

• Multicellular development relies on cell biomechanics and genetic/molecular signaling.
• Integrating these domains is key to understanding morphogenesis.
• Current models often lack a unified framework for both aspects.

Purpose of the Study:

• Introduce MecaGen, an integrative modeling platform.
• Enable hypothesis-driven simulation of developmental processes by coupling mechanical and chemical variables.
• Provide a unified framework for studying morphogenesis.

Main Methods:

• Developed MecaGen, a platform coupling mechanical and chemical variables.
• Utilized a minimal 'cell behavior ontology' (mesenchymal and epithelial cells).
• Enabled simulation of collective cell movements in 3D via gene regulatory networks and parameter exploration.

Main Results:

• Demonstrated MecaGen's validity and usefulness through three case studies.
• Investigated pattern formation, epithelial differentiation, and tissue tectonics in zebrafish.
• Validated simulations against live imaging data for tissue tectonics.

Conclusions:

• MecaGen offers a powerful, integrated approach to studying multicellular development.
• The platform facilitates understanding the interplay between physical forces and cell behaviors.
• MecaGen advances computational modeling in developmental biology and morphogenesis research.