Fig. 2.

Key mechanisms of FGF/FGFRs in the nervous system. The central nervous system comprises a large number of functionally and structurally diverse neuronal and glial cell types. The figure depicts model neurons forming synaptic connections as well as oligodendrocytes, astrocytes, and microglia. Modulation of synaptic connections by FGFs (boxed inset): FGF22 regulates the formation of excitatory synapses together with FGFR1b and R2b. Although both are involved in excitatory synapse regulation, inhibitory synapses are regulated by FGF7 via FGFR2b only. FGF2 and 20 synergise to regulate differentiation of dopaminergic neurons by using FGFR1IIIc as the receptor (FGF20 also binds to FGFR1IIIc in other neurons). When secreted by neurons, FGF2 enhances microglia activation, leading to increased removal of neuronal debris in case of neuronal damage. Moreover, FGF2 restores spatial learning, long-term potentiation, and neurogenesis in Alzheimer´s disease. Mechanistically, FGFR1 regulates CD200, which in turn mediates microglia responses and neurite outgrowth. This factor also feeds back by activation of FGFR1. Axonal growth and regeneration is stimulated mainly by FGF1 and FGF2. FGF2 secreted by neurons stimulates astrocytes via FGFR1-3 activation. Signalling from astrocytes to oligodendrocytes is accomplished by FGF2 influencing the survival and proliferation of oligodendrocyte precursor cells (OPCs). FGFR1 and R2 regulate myelin thickness and gene expression. For references, see text