title: 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.
authors.affiliation: EMBL, Meyerhofstrasse1, D-69117 Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Davidson
authors.forename: R
authors.initials: R
authors.lastname: Dono
authors.forename: R
authors.initials: R
authors.lastname: Zeller
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D015415:Biomarkers; D005346:Fibroblast Growth Factors