Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids

In this talk, I will present our recent work on the physical mechanisms underlying spontaneous axis formation in in vitro multicellular systems.

We use embryonic organoids called gastruloids, which recapitulate major processes of early mammalian development. Starting as 3D spherically symmetric aggregates of mouse or human embryonic stem cells, gastruloids undergo spontaneous symmetry breaking and develop an axial organization, with gene expression patterns that parallel front-back and dorso-ventral axes of the embryo in vivo. Gastruloids have attracted much attention in the biology community since their introduction about ten years and have been extensively studied and characterized, but almost exclusively from biochemical and genetic points of view. In contrast, little is known about the biophysical mechanisms contributing to their early organization.

In my presentation, I will present our recent work focusing on the collective tissue flows emerging during gastruloids symmetry breaking. By combining live two-photon imaging, image analysis, and physical modeling, we show that a dominating recirculating flow pattern reinforces the symmetry breaking by differentially advecting cells with different gene expression profiles. These observed flows are explained by a minimal hydrodynamic model, where flows are driven both by interface tensions between tissues with different gene expression and by tension differences at the surface in contact with the surrounding medium. While the separation of different cell populations through differential tension is an old idea, our experiments demonstrate for the first time that large-scale hydrodynamic flows contribute to such unmixing. I will also highlight how collective cell migration in gastruloids can be studied using 2.5D spreading assays.

In the last part of my talk, I will briefly mention ongoing projects in the team, including  our recent efforts to quantify cellular morphology, gene expression, and cell division patterns across gastruloids in 3D at the cellular scale, and also give an overview on the emergence of cardiac and vascular morphogenesis in older gastruloids.