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

Paul Cavanah, Junji Itou, Yudi Rusman, Naoyuki Tahara, Jessica M Williams, Christine E. Salomon, Yasuhiko Kawakami

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalDevelopmental Dynamics
DOIs
StateAccepted/In press - 2020

Keywords

  • Colomitide C
  • fibroblast growth factor signaling
  • fin regeneration
  • natural product
  • WNT signaling
  • zebrafish larvae

PubMed: MeSH publication types

  • Journal Article

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