Authors: SuMei Tsai DaWei Liu WenPin Wang
Publish Date: 2012/07/22
Volume: 22, Issue: 2, Pages: 301-314
Abstract
In mammals fibroblast growth factor FGF signaling controls liver specification and regulates the metabolism of lipids cholesterol and bile acids FGF signaling also promotes hepatocyte proliferation and helps detoxify hepatotoxin during liver regeneration after partial hepatectomy However the function of Fgf in zebrafish liver is not yet well understood specifically for postnatal homeostasis The current study analyzed the expression of fgf receptors fgfrs in the liver of zebrafish We then investigated the function of Fgf signaling in the zebrafish liver by expressing a dominantnegative Fgf receptor in hepatocytes lfabpdnfgfr1egfp lfdnfr Histological analysis showed that our genetic intervention resulted in a small liver size with defected medial expansion of developing livers in transgenic Tg larvae Morphologically the liver lobe of lfdnfr adult fish was shorter than that of control Ballooning degeneration of hepatocytes was observed in fish as young as 3 months Further examination revealed the development of hepatic steatosis and cholestasis In adult Tg fish we unexpectedly observed increased livertobodyweight ratios with higher percentages of proliferating hepatocytes Considering all these findings we concluded that as in mammals in adult zebrafish the metabolism of lipid and bile acids in the liver are regulated by Fgf signaling Disruption of the Fgf signalmediated metabolism might indirectly affect hepatocyte proliferationWe thank M P Harris Max Planck Institute for Developmental Biology Tubingen Germany for the fgfr1 probe K Yamasu Department of Regulation Biology Faculty of Science Saitama University Japan for the fgfr2 fgfr3 and fgfr4 probes D Y Stainier Department of Biochemistry and Biophysics Programs in Developmental and Stem Cell Biology Genetics and Human Genetics Cardiovascular Research Institute University of California USA for the cp probe and the tol2 lfabpcfpntr plasmid K D Poss Department of Cell Biology and Howard Hughes Medical Institute Duke University Medical Center USA for the hsp70dnfgfr1egfp plasmid and K Kawakami Division of Molecular and Developmental Biology National Institute of Genetics Japan for the pCSTP plasmid We also thank JL Wu Institute of Cellular and Organismic Biology Academia Sinica Taiwan for providing the Tglfabpegfp fish and Taiwan Zebrafish Core Facility at Academia Sinica which is supported by National Science Council NSC 1002321B001030 for providing the Tghsp70dnfgfr1egfp fish The expenses of our research were covered by grants from NSC 1002311B320001 and Tzu Chi University TCMRCP9901301 to WP Wang
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