Fig. 2.

Asymmetric fluid flow converts cellular chirality to embryo-level asymmetry. (A) Schematic ventral view of a three-somite stage mouse embryo depicting the mouse left-right organizer (LRO) (the node; blue oval) at the posterior tip of the notochord (nc). A leftward fluid flow in the LRO (blue arrow) represses Dand5 on the left, causing derepression and activation of the Nodal pathway in the left LPM (L-LPM). Midline-expressed Lefty inhibits Nodal activity in the right LPM (R-LPM), thereby maintaining unilateral activity. (B) Close-up view of a section of the LRO showing central pit cells harboring posteriorly polarized motile cilia, which rotate clockwise when viewed ventrally. These cilia generate an overall leftward flow in the LRO. This flow is sensed by immotile and unpolarized sensory cilia on the surface of lateral crown cells. In a little-understood sensory pathway, flow signals on the left cause the post-transcriptional repression of Dand5, ultimately promoting left LPM initiation of the Nodal pathway. By contrast, Dand5 remains unrepressed in right-sided crown cells and so Nodal signals do not reach a level compatible with R-LPM Nodal pathway activation.