ZFIN ID: ZDB-PUB-120724-27
Fibroblast growth factor (Fgf) signaling pathway regulates liver homeostasis in zebrafish
Tsai, S.M., Liu, D.W., and Wang, W.P.
Date: 2013
Source: Transgenic Research   22(2): 301-314 (Journal)
Registered Authors: Tsai, Su-Mei
Keywords: zebrafish, fibroblast growth factor receptor (fgfr), hepatocyte, steatosis, cholestasis
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/growth & development*
  • Bile Acids and Salts/metabolism
  • Embryonic Development/genetics
  • Fibroblast Growth Factors/genetics*
  • Fibroblast Growth Factors/metabolism
  • Gene Expression Regulation, Developmental
  • Hepatocytes/cytology
  • Hepatocytes/metabolism
  • Homeostasis/genetics*
  • Lipid Metabolism
  • Liver/metabolism*
  • Receptors, Fibroblast Growth Factor/genetics*
  • Receptors, Fibroblast Growth Factor/metabolism
  • Signal Transduction
  • Transcription Factors
  • Zebrafish/genetics
  • Zebrafish/growth & development
PubMed: 22820869 Full text @ Transgenic. Res.

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 dominant-negative Fgf receptor in hepatocytes (lfabp:dnfgfr1-egfp, lf:dnfr). 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 lf:dnfr 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 liver-to-body-weight 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 signal-mediated metabolism might indirectly affect hepatocyte proliferation.