Paul Cavanah1, Junji Itou1,2,3, Yudi Rusman4, Naoyuki Tahara1,2,3, Jessica M Williams4, Christine E Salomon4, Yasuhiko Kawakami1,2,3. 1. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA. 2. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA. 3. Developmental Biology Center, University of Minnesota, Minneapolis, Minnesota, USA. 4. Center for Drug Design, University of Minnesota, Minneapolis, Minnesota, USA.
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.
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.
Authors: Christine Y Shiang; Yuan Qi; Bailiang Wang; Vladimir Lazar; Jing Wang; W Fraser Symmans; Gabriel N Hortobagyi; Fabrice Andre; Lajos Pusztai Journal: Breast Cancer Res Treat Date: 2009-12-19 Impact factor: 4.872
Authors: Lijoy K Mathew; Sumitra Sengupta; Atsushi Kawakami; Eric A Andreasen; Christiane V Löhr; Catherine A Loynes; Stephen A Renshaw; Randall T Peterson; Robert L Tanguay Journal: J Biol Chem Date: 2007-09-11 Impact factor: 5.157