Simulations of particle tracking in the oligociliated mouse node and implications for left-right symmetry-breaking...

The concept of internal anatomical asymmetry is familiar-usually in humans the heart is on the left and the liver is on the right; however, how does the developing embryo know to produce this consistent laterality? Symmetry-breaking initiates with left-right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However, the question of what converts this flow into left-right asymmetric development remains unanswered. A leading hypothesis is that flow transports morphogen-containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observe in wild-type and mutant experiments, we extend the open-source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two and 112 beating cilia. Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wild-type mouse embryos: uniformly random release, localized cilium stress-induced release and localized release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localized release model resulting in significant transport in the oligociliated embryo. This article is part of the Theo Murphy meeting issue 'Unity and diversity of cilia in locomotion and transport'.