Fibroblast growth factor-5 is expressed in Schwann cells and is not essential for motoneurone survival

Fibroblast growth factor-5 (FGF-5) is a putative target-derived survival factor for motoneurones as it is concentrated in the synaptic portions of skeletal muscles and because it promotes the survival of embryonic motoneurones in vitro. A variety of experimental approaches have been used to examine this possibility. The expression of FGF-5 in the neuromuscular system was analysed using the reverse transcription-polymerase chain reaction (RT-PCR). Both splice variants of FGF-5 were detected in adult rat skeletal muscle, sciatic nerve, and spinal cord. The expression of FGF-5 in skeletal muscle was up-regulated after denervation. At first sight this appears to be consistent with FGF-5 being a target-derived factor. However, FGF-5 protein was detected in Schwann cells, macrophages, vascular smooth muscle and endothelial cells, but not in muscle fibres. The absence of FGF-5 in muscle fibres nas confirmed by RT-PCR examination of isolated muscle fibres. Furthermore. FGF-5 protein was also not detected in denervated fibres, as would be expected for a neuronal survival factor. Denervation did however lead to up-regulation of FGF-5 in the Schwann cells of the distal nerve trunk. This may indicate that FGF-5 is either an autocrine regulator of Schwann cells or a Schwann cell-derived neurotrophic factor. The latter appears not to be the case for two reasons. First. the double-ligation technique was used to show that endogenous FGF-5 is not transported in motor axons. Second, stereological estimates of the number of motoneurones in an FGF-5 null mutant (Angora) mouse Failed to reveal any loss of motoneurones. Collectively these experiments suggest that FGF-5 is not a physiological regulator of motoneurones, and therefore raise the possibility that it is an autocrine regulator of Schwann cells. (C) 2001 IBRO. Published by Elsevier Science Ltd, All rights reserved.