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 was 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.
McGeachie
A B
AB
Koishi
K
K
Imamura
T
T
McLennan
I S
IS
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003714:Denervation; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*
C496450:Fgf5 protein, mouse; C496451:Fgf5 protein, rat; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors