Two rotating cilia in the node cavity are sufficient to break left–right symmetry in the mouse embryo

Abstract

Determination of left-right asymmetry in mouse embryos is achieved by a leftward fluid flow (nodal flow) in the node cavity that is generated by clockwise rotational movement of 200-300 cilia in the node. The precise action of nodal flow and how much flow input is required for the robust read-out of left-right determination remains unknown. Here we show that a local leftward flow generated by as few as two rotating cilia is sufficient to break left-right symmetry. Quantitative analysis of fluid flow and ciliary rotation in the node of mouse embryos shows that left-right asymmetry is already established within a few hours after the onset of rotation by a subset of nodal cilia. Examination of various ciliary mutant mice shows that two rotating cilia are sufficient to initiate left-right asymmetric gene expression. Our results suggest the existence of a highly sensitive system in the node that is able to sense an extremely weak unidirectional flow, and may favour a model in which the flow is sensed as a mechanical force.