FGF PLAYS A SUBTLE ROLE IN OLIGODENDROCYTE MAINTENANCE IN-VIVO

Numerous in vitro studies indicate that fibroblast growth factors (FGF s) play a role in both the development and maintenance of oligodendroc ytes, Addition of FGF to mature oligodendrocytes in culture was report ed to downregulate the expression of genes encoding proteins of the my elin sheath and to induce a loss of myelin compaction, In this study, a model was developed to functionally block FGF signaling in oligodend rocytes in vivo, by generating transgenic mice expressing a dominant-n egative FGF receptor (FGFR1), under the control of the myelin basic pr otein (MBP) promoter, To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these c ells, Subsequently, five independent transgenic Zincs (''MBP-FRD'') we re generated, Three lines expressing the highest level of the transgen e were further studied, Initial investigation by Western blot and ligh t microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains, However, ultrastructural analysis of mye linated optic nerve fibres from tyro independent MBP-FRD lines reveale d a significant increase in myelin thickness as a function of fibre di ameter for both transgenic lines (13% and 16% increase), This increase in myelin thickness was not accompanied by alterations in myelin comp action, These results support the idea that FGF signaling in oligodend rocytes plays a role in the modulation of axon myelination in vivo. (C ) 1997 Wiley-Liss, Inc.