Determining zebrafish dorsal organizer size by a negative feedback loop between canonical/non-canonical Wnts and Tlr4/NFκB

Juqi Zou, Satoshi Anai, Satoshi Ota, Shizuka Ishitani, Masayuki Oginuma and Tohru Ishitani ()
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Juqi Zou: Osaka University
Satoshi Anai: Yuuai Medical Center
Satoshi Ota: The University of Tokyo
Shizuka Ishitani: Osaka University
Masayuki Oginuma: Osaka University
Tohru Ishitani: Osaka University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42963-3

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