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.
Bibliographical noteFunding Information:
The authors declare no competing interest. We are grateful to Drs. James Amatruda, Richard Dorsky, Stephen Ekker, Enrico Moro and Angel Raya for sharing zebrafish lines, to Dr. Michael O'Connor for sharing his equipment, to Dr. Anindya Bagchi for helpful discussion, and to the Zebrafish Core Facility at the University of Minnesota for the help with zebrafish husbandry. We also thank Nicole Kilby, Tyler Burgoyne, Tyler Willing, Michael Brush, An Le, Sho Kawakami and Dr. Robyn Leary for their excellent assistance. This study was supported by the University of Minnesota Center for Drug Design Seed Grant to CES (CDD2013) and a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health to YK (R01AR064195). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts to disclose.
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- Colomitide C
- WNT signaling
- fibroblast growth factor signaling
- fin regeneration
- natural product
- zebrafish larvae