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.
Highlights
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
The genetic and signalling aspect of developmental biology can be summarized by the formal concept of gene regulatory network (GRN), which shifts the focus from single genes to molecular interactions among multiple genes and signalling pathways[14]
To demonstrate how MecaGen allows the study of molecular cues that can both direct the specification of motile behaviour and coordinate the displacements of thousands of individual cells, we model here the first phase of epiboly in the zebrafish embryo, an episode occurring between 3.7 h postfertilization and 5.3 hpf (50%-epiboly stage)[43]
Summary
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. We present an integrated computational model and simulation platform of these dual processes, called MecaGen. On the one hand, cell biomechanics investigates how physical forces and deformations exerted and sustained by cells progressively transform the embryo, defining morphogenesis[2]. The model needs to include the influence of forces on signals through the deformation and mechanical stress of the cellular tissue due to local cell rearrangements, which modify the signalling environment via ligand-gated transduction and mechanotransduction
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