Fibroblast growth factor 2 regulates astrocyte differentiation in a region-specific manner in the hindbrain.

Fibroblast growth factor (FGF)-2 is known to have important pleiotropic effects in neuronal and glial cells during various physiological and pathological events. To investigate the role of endogenous FGF-2 in the differentiation of astrocytes, we studied the expression of glial fibrillary acidic protein (GFAP) in the hindbrain of the FGF-2 null mouse. GFAP was drastically decreased in a region-specific manner in the hindbrain of the adult and developing FGF-2 null mouse without an associated change in the expression of alternate markers for astrocytes. The deficit was evident in the astrocytes of pontine and medullary gray matter but not in the white matter. The astrocytes of the gray and white matter were seen to express FGF-2 and FGF receptors in a distinct pattern. The methylation of histone H3 at lysine 4 residue (H3K4me2) associated with the STAT (signal transducer and activator of transcription)-binding site of the GFAP promoter was significantly decreased in the gray matter of the FGF-2 null mouse, suggesting a role for FGF-2 in the epigenetic regulation of astrocyte differentiation in vivo. These observations underscore the importance of FGF-2 in astroglial differentiation in the hindbrain and the heterogeneity of astrocytes in their requirement for FGF-2 as a differentiation inducing signal.