Multi-tissue mechanics in the development and engineering of the posterior body axis (360G-Wellcome-225360_Z_22_Z)

During development tissues wrapped in extra-cellular matrix (ECM) undergo well-defined deformations to build an embryo. How morphogenetic provides mechanical forces to control the shaping of adjacent tissues is unknown. However, a clear understanding of multi-tissue mechanics is essential to engineer the morphogenesis of organoids in vitro if we wish to use these structures to accurately model their in vivo counterparts. Vertebrate posterior body elongation exemplifies the problem of multi-tissue morphogenesis as the shaping of the notochord, spinal cord and somitic mesoderm must be coordinated together generate a proportioned body axis. We will measure how mechanical forces impacting upon the zebrafish pre-somitic mesoderm alter when spinal cord and notochord expansion is disrupted and characterize the impact on tissue elongation and signalling. A second aim will model pre-somitic mesoderm elongation in aggregates of mouse embryonic stem cells or gastruloids. By modulating the stiffness and ECM composition surrounding the organoid, we will assess their impact on mesoderm progenitor self-renewal. Finally, we will recapitulate in vivo multi-tissue mechanics by encapsulating gastruloids in matrix and applying compressive forces using micro-cantilevers and microfluidics. It will enable a reciprocal interaction between developmental biology and bioengineering in developing new approaches to engineer improved morphology of multicellular systems.