Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids

Abstract

During the early development of multi-cellular animals, cells self-organize to set up the body axes such as the primary head-to-tail axis. Several signalling pathways are known to control body axis formation. Here we show that tissue mechanics also plays an important role. We focus on the emergence of a primary axis in initially spherical aggregates of mouse embryonic stem cells, which mirrors events in the development of the early mouse embryo. These aggregates break rotational symmetry by establishing domains of different expression profiles, for example, of the transcription factor T/Brachyury and the adhesion molecule E-cadherin. By combining quantitative microscopy and physical modelling, we identify large-scale tissue flows with a recirculating component that contribute substantially to the symmetry breaking. We show that the recirculating flows are—akin to Marangoni flows—driven by a difference in tissue surface tensions, whose existence we further confirm using aggregate fusion experiments. Our work highlights that body axis formation is not only driven by biochemical processes but can also be amplified by tissue flows. We expect that this type of amplification may operate in many other organoid and in vivo systems.