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

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.