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.

Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA

“…7f) of 1% methylcellulose. As reported previously 16 , 1% methylcellulose completely abolishes the flow (see Supplementary Fig. S10).…”

“…4k). These results thus indicated that Wnt signalling activity becomes asymmetric slightly later than does expression of Cerl2 (late headfold stage to 1 pss) 16 . To examine the role of asymmetric Wnt signalling around the node in asymmetric expression of Cerl2, we examined the effect of conditional deletion of the b-catenin gene by crossing bcatenin flox/flox mice with ROSA CreERT2/ þ , bcatenin flox/ þ mice 17 .…”

Roles of Motile and Immotile Cilia in Left-Right Symmetry Breaking

“…However, none of them fulfill the requirements for the determinant. On the other hand, many lines of circumstantial evidence, including the recent observation that as few as two rotating cilia are sufficient for the breaking of L-R symmetry [19], favor the latter model. However, it is still not clear what exactly the immotile cilia sense during the symmetry-breaking event.…”

“…Cerl2 is the most immediate readout of the flow signal [19,20]. Cerl2 encodes a Nodal antagonist, although its precise action is not clear.…”

Sperm dysfunction and ciliopathy

“…They are tilted posteriorly and show rotational movement. The flow caused by nodal cilia determines leftright asymmetry [83][84][85]. Two types of cells are found in the node: pit cells and crown cells.…”