Migrating mesoderm cells self-organize into a dynamic meshwork structure during chick gastrulation

Migration of cell populations is a fundamental process in morphogenesis and disease. The mechanisms of collective cell migration of epithelial cell populations have been well studied. It remains unclear, however, how the highly motile mesenchymal cells, which migrate extensively throughout the embryo, are connected with each other and coordinated as a collective. During gastrulation in chick embryos, the mesoderm cells, that are formed by an epithelial-to-mesenchymal transition (EMT), migrate in the 3D space between ectoderm and endoderm of the embryo. Using live imaging and quantitative analysis, such as topological data analysis (TDA), we found that the mesoderm cells undergo a novel form of collective migration, in which they form a meshwork structure while moving away from the primitive streak. This meshwork is supported by N-cadherin-mediated cell-cell adhesion, which undergoes rapid reorganization. Overexpressing a mutant form of N-cadherin decreases the speed of tissue progression and the directionality of the collective cell movement, whereas the speed of individual cells remains unchanged. To investigate how this meshwork arises and how it contributes to the cell movement, we utilized an agent-based theoretical model, showing that cell elongation, cell-cell adhesion, and cell density are the key parameters for the meshwork formation. These data provide novel insights into how a supracellular structure of migrating mesenchymal cells forms and how it facilitates efficient migration during early mesoderm formation.