Expression of the fibroblast growth factor family and their receptor family genes during mouse brain development.
The fibroblast growth factor (FGF) family is composed of nine members and four genes encode protein tyrosine kinase receptors for them. To gain insight into the involvement of FGFs and their receptors in the development of nervous system, their expression in brains of perinatal and adult mice was examined by semi-quantitative reverse transcription-linked polymerase chain reactions and in situ hybridization. Although all the genes, with the exception of FGF-4, were found to be expressed, FGF-3, FGF-6, FGF-7 and FGF-8 genes demonstrated higher expression in the late embryonic stages than in postnatal stages, suggesting that these members are involved in the late stages of brain development. In contrast, expression of FGF-1 and FGF-5 increased after birth. Interestingly, FGF-6 expression in perinatal mice was restricted to the central nervous system and skeltal muscles, with intense signals in the developing cerebrum in embryos but in cerebellum in 5-day-old neonates. Furthermore, FGF-receptor (FGFR)-4, a cognate receptor for FGF-6, demonstrated similar spatiotemporal expression, suggesting that FGF-6 and FGFR-4 plays significant roles in the maturation of nervous system as a ligand-receptor system. The results indicate that individual member of the fibroblast growth factor and their receptor family are expressed either sequentially or simultaneously in brain development, strongly suggesting their involvement in the regulation of a variety of developmental processes of brain, i.e., proliferation and migration of neuronal progenitor cells, neuron and glia differentiation, neurite extensions, and synapse formations.