RRC ID |
79205
|
Author |
Zou J, Anai S, Ota S, Ishitani S, Oginuma M, Ishitani T.
|
Title |
Determining zebrafish dorsal organizer size by a negative feedback loop between canonical/non-canonical Wnts and Tlr4/NFκB.
|
Journal |
Nat Commun
|
Abstract |
In vertebrate embryos, the canonical Wnt ligand primes the formation of dorsal organizers that govern dorsal-ventral patterns by secreting BMP antagonists. In contrast, in Drosophila embryos, Toll-like receptor (Tlr)-mediated NFκB activation initiates dorsal-ventral patterning, wherein Wnt-mediated negative feedback regulation of Tlr/NFκB generates a BMP antagonist-secreting signalling centre to control the dorsal-ventral pattern. Although both Wnt and BMP antagonist are conserved among species, the involvement of Tlr/NFκB and feedback regulation in vertebrate organizer formation remains unclear. By imaging and genetic modification, we reveal that a negative feedback loop between canonical and non-canonical Wnts and Tlr4/NFκB determines the size of zebrafish organizer, and that Tlr/NFκB and Wnts switch initial cue and feedback mediator roles between Drosophila and zebrafish. Here, we show that canonical Wnt signalling stimulates the expression of the non-canonical Wnt5b ligand, activating the Tlr4 receptor to stimulate NFκB-mediated transcription of the Wnt antagonist frzb, restricting Wnt-dependent dorsal organizer formation.
|
Volume |
14(1)
|
Pages |
7194
|
Published |
2023-11-8
|
DOI |
10.1038/s41467-023-42963-3
|
PII |
10.1038/s41467-023-42963-3
|
PMID |
37938219
|
PMC |
PMC10632484
|
MeSH |
Animals
Drosophila
Feedback
Ligands
NF-kappa B*
Wnt Signaling Pathway
Zebrafish*
|
IF |
12.121
|
Resource |
Zebrafish |
Tg(6xTcf/LefBS-miniP:d2EGFP)(Tg(OTM:d2EGFP))
Tg(6xNFκB BS-tkP:D2EGFP)
rela-A |