Uncovering the mechanisms that time progenitor contributions to the elongating body axis in vertebrate embryos

During vertebrate body axis elongation, populations of progenitor cells in the posterior-most tailbud region of the embryo continually make choices about which cell type they should differentiate into. These decisions must be carefully balanced against the rates of expansion of anterior structures such as the spinal cord, notochord and somites so that a well-proportioned body axis is generated. We hypothesise that anterior tissue expansion generates force production in the tailbud that is sensed by the progenitors to regulate their rates of differentiation and movement. We have preliminary data showing the activation of key mechano-transduction pathways within the tailbud, and mutant zebrafish lines where regulators of this pathway are disrupted. The project will characterise these mutants using light-sheet imaging to test the hypothesis that cells actively respond to changes in their mechanical environment to time their addition to the elongating body axis.

We are also interested in developing projects using chick embryos as a model where we can ask how the timing of progenitor contribution is alters as the progenitor domain matures during development. In parallel we make us of embryonic organoids from mouse embryonic stem cells (gastruloids) to experimentally manipulate the mechanical and metabolic environment of cells to test how these factors modulate the timing of mesoderm cell migration and differentiation.