Elongation mechanics in vertebrate embryos – ElongMech

We aim to combine cell motion with tissue rheology to shed light on the axis elongation process. Cell tracking is therefore used to characterize tissue flow along the anterior-posterior axis of a chicken embryo. The rheological properties of the presomtic mesoderm and adjacent tissues are studies using microaspirating techniques.

Cells inside the presomitic mesoderm have a gradient of diffusion along the major axis of the embryo. This gradient is correlated with the elongation rate of the tail, and can be controlled by modifying cell activity. The prismatic mesoderm behaves like a viscoelastic liquide.

Our focus is to combine experimentally measured mechanical parameters such as cell motility, tissue viscoelasticity and expansion forces, with theoretical modeling to describe a morphogenetic phenomenon not yet fully understood. It has the potential to be applied to other events in vertebrate development where tissue extension occurs through cells diffusion and not directed cell motion.

In progress

Early stages of embryonic morphogenesis are characterized by large-scale tissue movements, giving rise to the formation of body axis, and apparition of various tissues destined to form specific organs. In the vertebrate embryo, once the anterio-posterior axis is specified, the body axis elongates by addition of progenitor cells into the posterior growth zone known as the presomitic mesoderm (PSM). While the tissue elongates, these highly motile mesenchymal cells slow down and undergo mesenchymal to epithelial transition. They then condense to form the epithelial tissue segments called somites, which later develop into dermis, skeletal muscles and vertebrae. Detailed studies of the biochemical process involved in segmentation reveal that the cyclic expression of genes, known as the segmentation clock, set the tempo for somite formation, whereas the position of each somite is dictated by gradients of various morphogens, such as the fibroblast growth factor (FGF8).

Recent investigations have demonstrated that the ablation of the posterior PSM halts the elongation process, pointing to the importance of the PSM in the elongation process. Moreover, the cells inside the PSM do not show a directional motion; instead they diffuse randomly, with a diffusion coefficient that correlates with the concentration of FGF8. It is proposed that a gradient in cell diffusion is the cause of the symmetry breaking process, which results in the elongation of the axis from the posterior side. It is now necessary to investigate the physical mechanisms involved in elongation and to identify and quantify the factors that control mechanically this process.

We propose to study the mechanics of axis elongation in chicken embryo using techniques and concepts used in soft matter physics, and combine them with biological approaches. More precisely our goal is to quantify tissue flow and elongation forces as a function of cell activity and motility, and to explore the role of the visco-elasticity of the PSM in regulating cell motility.

The findings of this project will allow us to directly evaluate the role of the cellular diffusion gradient in the control of the axis elongation and further enable the modeling of the physical properties governing the axis elongation in vertebrates. The greater impact of the proposed project will be to help us better understands the physical mechanisms that can play a role in various pathologies such as congenital defects of lower limbs.