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XB-ART-58455
Nat Commun January 1, 2021; 12 (1): 5482.

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

Maerker M , Getwan M , Dowdle ME , McSheene JC , Gonzalez V , Pelliccia JL , Hamilton DS , Yartseva V , Vejnar C , Tingler M , Minegishi K , Vick P , Giraldez AJ , Hamada H , Burdine RD , Sheets MD , Blum M , Schweickert A .


Abstract
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.

PubMed ID: 34531379
PMC ID: PMC8446035
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bicc1 dand5 dicer1 gdf3 myod1 nodal nodal1 pitx2 pkd2
GO keywords: RNA binding [+]
Morpholinos: bicc1 MO1 bicc1 MO2 bicc1 MO3 bicc1 MO4 dand5 MO3 dand5 MO4 dand5 MO5 dand5 MO6 dand5 MO7 dicer1 MO5 dicer1 MO6 gdf3 MO1

Phenotypes: Xla Wt + bicc1 (Fig. 3 C ) [+]

Article Images: [+] show captions