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