Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5.
3' Untranslated Regions
/ genetics
Animals
Body Patterning
/ genetics
Embryonic Development
/ genetics
Gene Expression Regulation, Developmental
Intercellular Signaling Peptides and Proteins
/ genetics
Mice
RNA Stability
/ genetics
RNA-Binding Proteins
/ genetics
Ribonuclease III
/ genetics
Xenopus laevis
/ embryology
Zebrafish
/ embryology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 09 2021
16 09 2021
Historique:
received:
13
01
2020
accepted:
11
08
2021
entrez:
17
9
2021
pubmed:
18
9
2021
medline:
21
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34531379
doi: 10.1038/s41467-021-25464-z
pii: 10.1038/s41467-021-25464-z
pmc: PMC8446035
doi:
Substances chimiques
3' Untranslated Regions
0
Intercellular Signaling Peptides and Proteins
0
RNA-Binding Proteins
0
Ribonuclease III
EC 3.1.26.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5482Subventions
Organisme : NICHD NIH HHS
ID : R01 HD091921
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007388
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021. The Author(s).
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