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Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. Ciliary activity of the calcium channel Pkd2 is crucial for flow sensing. How this flow signal is further processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed that flow down-regulates mRNA expression of the Nodal inhibitor Dand5 in left sensory cells. De-repression of the co-expressed Nodal, complexed with the TGFß growth factor Gdf3, drives LPM Nodal cascade induction. Here, we show that post-transcriptional repression of  dand5  is a central process in symmetry breaking of  Xenopus , zebrafish and mouse. The RNA binding protein Bicc1 was identified as a post-transcriptional regulator of  dand5  and  gdf3  via their 3′-UTRs. Two distinct Bicc1 functions on  dand5  mRNA were observed at pre- and post-flow stages, affecting mRNA stability or flow induced translational inhibition, respectively. To repress  dand5 , Bicc1 co-operates with Dicer1, placing both proteins in the process of flow sensing. Intriguingly, Bicc1 mediated translational repression of a  dand5  3′-UTR mRNA reporter was responsive to  pkd2 , suggesting that a flow induced Pkd2 signal triggers Bicc1 mediated  dand5  inhibition during symmetry breakage.

Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5