@article{85271,
  author = {Markus Maerker and Maike Getwan and Megan Dowdle and Jason McSheene and Vanessa Gonzalez and Jos{\'e} Pelliccia and Danielle Hamilton and Valeria Yartseva and Charles Vejnar and Melanie Tingler and Katsura Minegishi and Philipp Vick and Antonio Giraldez and Hiroshi Hamada and Rebecca Burdine and Michael Sheets and Martin Blum and Axel Schweickert},
  title = {Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5.},
  abstract = {<p>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 TGF{\ss} 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{\textquoteright}-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{\textquoteright}-UTR mRNA reporter was responsive to pkd2, suggesting that a flow induced Pkd2 signal triggers Bicc1 mediated dand5 inhibition during symmetry breakage.</p>},
  year = {2021},
  journal = {Nature communications},
  volume = {12},
  pages = {5482},
  month = {09/2021},
  issn = {2041-1723},
  doi = {10.1038/s41467-021-25464-z},
  language = {eng},
}