Uncovering the mechanochemical signalling inputs that drive gastruloid axial patterning

Description

How the early mammalian embryo converts a mass of identical cells in an organism with multiple axes of symmetry (anteroposterior, dorsoventral, mediolateral) is a critical question in developmental biology. Traditional approaches using forward and reverse genetics in animal models have elucidated many of the signals that specify these processes, however it is still unknown how the embryo integrates both mechanical and chemical signals over time, and how these impact cell fate allocation and morphogenesis.

To get a better understanding of these processes, this project will take an innovative in vitro organoid approach using gastruloids as an experimental system. Gastruloids are 3D aggregates of mouse embryonic stem cells, mimic many embryonic patterning events in culture, and critically they develop all embryonic axes in culture. The highly-controlled and scalable nature of gastruloids provides the means to access, observe and quantify the unfolding of early developmental patterning in detail.

The successful applicant will utilise gastruloids to uncover how signals (such as Wnt, Notch, and Nodal) work in concert with mechanical signals to robustly specify cell fate and pattern formation. They will use quantitative microscopy of fixed and live gastruloids, following reporter and protein dynamics in real time, assessing how specific inputs alter cell fate.