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

TL;DR

This study uses simulations of particle transport in the mouse embryo's ventral node to explore mechanisms of left-right asymmetry, finding that random morphogen release best explains observed developmental patterns.

Contribution

It extends the NEAREST hydrodynamics package to model particle motion in cilia-driven flows, testing different morphogen release hypotheses against experimental data.

Findings

Random particle release aligns with observed asymmetry patterns.

Localized release models do not produce sufficient transport in oligociliated embryos.

Hydrodynamic simulations support the hypothesis of random morphogen distribution.

Abstract

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 hypotheses 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 observed in wildtype 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 wildtype mouse embryos: uniformly random release, localised cilium stress induced release, and localised release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localised-release model resulting in significant transport in the oligociliated embryo.