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

TitleBicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5.
Publication TypeJournal Article
Year of Publication2021
AuthorsMaerker, 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
JournalNat Commun
Date Published2021 09 16
Keywords3' Untranslated Regions, Animals, Body Patterning, Embryonic Development, Gene Expression Regulation, Developmental, Intercellular Signaling Peptides and Proteins, Mice, Ribonuclease III, RNA Stability, RNA-Binding Proteins, Xenopus laevis, Zebrafish

<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 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.</p>

Alternate JournalNat Commun
PubMed ID34531379
PubMed Central IDPMC8446035
Grant ListR01 HD091921 / HD / NICHD NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
UL1 TR001863 / TR / NCATS NIH HHS / United States