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A nontoxic fungal natural product modulates fin regeneration in zebrafish larvae upstream of FGF‐WNT developmental signaling
Author(s) -
Cavanah Paul,
Itou Junji,
Rusman Yudi,
Tahara Naoyuki,
Williams Jessica M.,
Salomon Christine E.,
Kawakami Yasuhiko
Publication year - 2021
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.244
Subject(s) - biology , zebrafish , fibroblast growth factor , regeneration (biology) , microbiology and biotechnology , wnt signaling pathway , developmental biology , blastema , signal transduction , biochemistry , receptor , gene
Abstract Background The regeneration of larvae zebrafish fin emerged as a new model of regeneration in the last decade. In contrast to genetic tools to study fin regeneration, chemical probes to modulate and interrogate regeneration processes are not well developed. Results We set up a zebrafish larvae fin regeneration assay system and tested activities of natural product compounds and extracts, prepared from various microbes. Colomitide C, a recently isolated product from a fungus obtained from Antarctica, inhibited larvae fin regeneration. Using fluorescent reporter transgenic lines, we show that colomitide C inhibited fibroblast growth factor (FGF) signaling and WNT/β‐catenin signaling, which were activated after larvae fin amputation. By using the endothelial cell reporter line and immunofluorescence, we showed that colomitide C did not affect migration of the blood vessel and nerve into the injured larvae fin. Colomitide C did not show any cytotoxic activities when tested against FGF receptor‐amplified human cancer cell lines. Conclusion Colomitide C, a natural product, modulated larvae fin regeneration likely acting upstream of FGF and WNT signaling. Colomitide C may serve as a template for developing new chemical probes to study regeneration and other biological processes.