Fibroblast growth factor 10 is critical for liver growth during embryogenesis and controls hepatoblast survival via beta-catenin activation

Hepatology. 2007 Oct;46(4):1187-97. doi: 10.1002/hep.21814.


Fibroblast growth factor (FGF) signaling and beta-catenin activation have been shown to be crucial for early embryonic liver development. This study determined the significance of FGF10-mediated signaling in a murine embryonic liver progenitor cell population as well as its relation to beta-catenin activation. We observed that Fgf10(-/-) and Fgfr2b(-/-) mouse embryonic livers are smaller than wild-type livers; Fgf10(-/-) livers exhibit diminished proliferation of hepatoblasts. A comparison of beta-galactosidase activity as a readout of Fgf10 expression in Fgf10(+/LacZ) mice and of beta-catenin activation in TOPGAL mice, demonstrated peak Fgf10 expression from E9 to E13.5 coinciding with peak beta-catenin activation. Flow cytometric isolation and marker gene expression analysis of LacZ(+) cells from E13.5 Fgf10(+/LacZ) and TOPGAL livers, respectively, revealed that Fgf10 expression and beta-catenin signaling occur distinctly in stellate/myofibroblastic cells and hepatoblasts, respectively. Moreover, hepatoblasts express Fgfr2b, which strongly suggests they can respond to recombinant FGF10 produced by stellate cells. Fgfr2b(-/-)/TOPGAL(+/+) embryonic livers displayed less beta-galactosidase activity than livers of Fgfr2b(+/+)/TOPGAL(+/+) littermates. In addition, cultures of whole liver explants in Matrigel or cell in suspension from E12.5 TOPGAL(+/+)mice displayed a marked increase in beta-galactosidase activity and cell survival upon treatment with recombinant FGF10, indicating that FGFR (most likely FGFR2B) activation is upstream of beta-catenin signaling and promote hepatoblast survival.

Conclusion: Embryonic stellate/myofibroblastic cells promote beta-catenin activation in and survival of hepatoblasts via FGF10-mediated signaling. We suggest a role for stellate/myofibroblastic FGF10 within the liver stem cell niche in supporting the proliferating hepatoblast.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Survival / physiology
  • Cells, Cultured
  • Embryonic Development / genetics
  • Embryonic Development / physiology*
  • Fibroblast Growth Factor 10 / genetics
  • Fibroblast Growth Factor 10 / metabolism*
  • Gene Expression Regulation, Developmental
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Liver / cytology
  • Liver / embryology*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Signal Transduction / physiology
  • beta Catenin / genetics
  • beta Catenin / metabolism*
  • beta-Galactosidase / metabolism


  • Fgf10 protein, mouse
  • Fibroblast Growth Factor 10
  • beta Catenin
  • Receptor, Fibroblast Growth Factor, Type 2
  • beta-Galactosidase