PUBLICATION

A nontoxic fungal natural product modulates fin regeneration in zebrafish larvae upstream of FGF-WNT developmental signaling

Authors
Cavanah, P., Itou, J., Rusman, Y., Tahara, N., Williams, J.M., Salomon, C.E., Kawakami, Y.
ID
ZDB-PUB-200829-14
Date
2020
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   250(2): 160-174 (Journal)
Registered Authors
Kawakami, Yasuhiko
Keywords
Colomitide C, Fibroblast growth factor signaling, WNT signaling, fin regeneration, natural product, zebrafish larvae
MeSH Terms
  • Animal Fins
  • Animals
  • Biological Products/pharmacology
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Drug Evaluation, Preclinical
  • Fibroblast Growth Factors/metabolism
  • Humans
  • Regeneration/drug effects*
  • Wnt Signaling Pathway/drug effects
  • Zebrafish
PubMed
32857425 Full text @ Dev. Dyn.
Abstract
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.
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.
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. This article is protected by copyright. All rights reserved.
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