Lack of keratinocyte growth factor retards angiogenesis in cutaneous wounds.

This study investigated the effects of keratinocyte growth factor (KGF) on wound healing. Full-thickness excisional dorsal wounds were created on KGF knockout mice (KGF KO, n = 12) and wild-type C57BL/6 mice (WT, n = 12), and wound closure rates were measured. Immunohistochemical staining was used to investigate cell proliferation and blood vessel density by assessing Ki67 and CD31 protein levels, respectively, and real-time reverse transcription-polymerase chain reaction was used to measure vascular endothelial growth factor (VEGF) mRNA levels. No differences in the rate of wound closure were found between KGF KO and WT mice, however the KGF KO mice showed decreased proliferation of keratinocytes, angiogenesis and VEGF mRNA levels in vivo. These results suggest that KGF may play an important role in the regulation of VEGF gene expression and angiogenesis during wound healing.

Distinct FGFs promote differentiation of excitatory and inhibitory synapses.

The differential formation of excitatory (glutamate-mediated) and inhibitory (GABA-mediated) synapses is a critical step for the proper functioning of the brain. An imbalance in these synapses may lead to various neurological disorders such as autism, schizophrenia, Tourette's syndrome and epilepsy. Synapses are formed through communication between the appropriate synaptic partners. However, the molecular mechanisms that mediate the formation of specific synaptic types are not known. Here we show that two members of the fibroblast growth factor (FGF) family, FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. FGF22 and FGF7 are expressed by CA3 pyramidal neurons in the hippocampus. The differentiation of excitatory or inhibitory nerve terminals on dendrites of CA3 pyramidal neurons is specifically impaired in mutants lacking FGF22 or FGF7. These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. FGF22-deficient mice are resistant to epileptic seizures, and FGF7-deficient mice are prone to them, as expected from the alterations in excitatory/inhibitory balance. Differential effects of FGF22 and FGF7 involve both their distinct synaptic localizations and their use of different signalling pathways. These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain.