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

Abstract

The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal ‘cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework.

Mechanisms of cell polarization

“…While we are beginning to study larger networks (described further on), challenges remain in developing techniques to analyze their behavior. A recent example with potential to explore the interactions of genes, mechanical forces, and multicellular interactions is the open source platform MecaGen [116]. …”

An integrated modelling framework from cells to organism based on a cohort of digital embryos

“…Relying on the above digital reconstruction and probabilistic model, the last stage of our study consisted of a spatially explicit computational model and simulation of the sea urchin embryo based on the MecaGen platform18. In a nutshell, it was designed as a particle-based model, where the interactions between cells were decomposed into an attraction-repulsion component and a planarity conservation component.…”

“…The MecaGen modelling platform was published as an open source software18. The scripts for the statistical analysis and for the construction of the prototype from empirical data are provided here as a MATLAB library (Supplementary Software 1).…”

“…Analysing the large amount of data generated by such tools requires novel methodological approaches13141516. We combined data organisation, multi-level probabilistic modelling and data fusion techniques, applied to measurable parameters, with spatially explicit biomechanical modelling1718 to infer the remaining free parameters. This hybrid strategy led to a realistic prototypical simulation of the sea urchin lineage tree and developing embryo in 3D, directly comparable to empirical data.…”

Multiscale mechanical model for cell division orientation in developing biological systems

“…In a developing biological system several dynamical processes take place at specific positions in order to produce and change the system's shape. These local processes leading to shape changes need either to be tightly coordinated or dynamically adjusted to ensure global coherence [1][2][3]. There must hence exist mechanisms through which shape dynamics information is transferred and read.…”