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

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