Fibroblast growth factors in the developing central nervous system

1. It is now clear that members of the fibroblast growth factor (FGF) family have multiple roles during the formation of the central nervous system (CNS). 2. There are at least 23 members of the FGF family and, of these, 10 are expressed in the developing CNS, along with four FGF receptors (FGFR-1-4). 3. The present review discusses the roles of these FGFs, with emphasis on FGF-2, FGF-8, FGF-15 and FGF-17. Fibroblast growth factors-2 and -15 are generally expressed throughout the developing CNS, whereas FGF-8 and FGF-17 are tightly localized to specific regions of the developing brain and are only expressed in the embryo during the early phases of proliferation and neurogenesis. 4. Expression studies on FGFRs in the chick and mouse indicate that FGFR-1 is most generally expressed, whereas FGFR-2 and FGFR-3 show highly localized but changing patterns of expression throughout CNS development. The FGFR-4 has been localized to the developing CNS in fish but not at a detailed level, as yet, in chick or mouse. 5. A picture is emerging from these studies that particular FGFs signal through specific receptors in a highly localized manner to regulate the development of different regions of the brain. 6. This picture has been demonstrated so far for the developing cortex (FGF-2-/- mice), the forebrain and midbrain (FGF-8 hypomorphs) and the cerebellum (FGF-17/FGF-8 mutant mice). In addition, generation of mutant animals deleted for FGFR-1 and FGFR-2b IIIb demonstrate their importance in FGF signalling. 7. However, there are significant gaps in our knowledge of the localization of members of the FGF family and their receptors. More detailed information on the spatio-temporal mapping of FGFs and FGFR isoforms is required in order to understand the molecular mechanisms through which FGFs signal.