Viscosity-mediated signal amplification enables robust left-right symmetry breaking in the mouse node

Abstract

Left-right (LR) symmetry breaking in vertebrates depends on a directional fluid flow generated in the embryonic LR organizer, yet how this flow is sensed remains unresolved. Mechanosensing and chemosensing models each capture part of the process but face key limitations when considered independently. Here, we introduce a minimal theoretical model of viscosity-mediated signal amplification that unifies these perspectives. In this framework, macromolecules secreted by organizer cells locally increase the near-surface viscosity, creating another viscous fluid layer that is entrained by the leftward nodal flow. This layer can significantly amplifies the drag and torque exerted on immotile perinodal cilia, enabling robust discrimination of flow direction even when flow magnitudes on the left and right are nearly identical. The model naturally incorporates macromolecule secretion, clarifies the complementary roles of motile and immotile cilia, and resolves the major shortcomings of previous proposals. Together, these results provide a simple and physically grounded mechanism for LR determination in the mouse node.