FGF signalling is required for differentiation-induced cytoskeletal reorganisation and formation of actin-based processes by podocytes

J Cell Sci. 2001 Sep;114(Pt 18):3359-66.

Abstract

To examine the potential role of fibroblast growth factor (FGF) signalling during cell differentiation, we used conditionally immortalised podocyte cells isolated from kidneys of Fgf2 mutant and wild-type mice. Wild-type mouse podocyte cells upregulate FGF2 expression when differentiating in culture, as do maturing podocytes in vivo. Differentiating wild-type mouse podocyte cells undergo an epithelial to mesenchymal-like transition, reorganise their actin cytoskeleton and extend actin-based cellular processes; all of these activities are similar to the activity of podocytes in vivo. Molecular analysis of Fgf2 mutant mouse podocyte cells reveals a general disruption of FGF signalling as expression of Fgf7 and Fgf10 are also downregulated. These FGF mutant mouse podocyte cells in culture fail to activate mesenchymal markers and their post-mitotic differentiation is blocked. Furthermore, mutant mouse podocyte cells in culture fail to reorganise their actin cytoskeleton and form actin-based cellular processes. These studies show that FGF signalling is required by cultured podocytes to undergo the epithelial to mesenchymal-like changes necessary for terminal differentiation. Together with other studies, these results point to a general role for FGF signalling in regulating cell differentiation and formation of actin-based cellular processes during morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Biomarkers
  • Cell Differentiation / physiology
  • Cell Line, Transformed / cytology
  • Cell Line, Transformed / metabolism
  • Cytoskeleton / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Kidney Glomerulus / cytology
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Mice
  • Mice, Mutant Strains / genetics
  • Mice, Mutant Strains / metabolism
  • Morphogenesis / physiology
  • Signal Transduction / physiology

Substances

  • Actins
  • Biomarkers
  • Fibroblast Growth Factors