Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons.
Muscle-derived factors are known to be important for the survival of developing spinal motoneurons, but the molecules involved have not been characterized. Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in muscle development and motoneuron axon outgrowth. We show that HGF/SF has potent neurotrophic activity (EC50=2 pM) for a subpopulation (40%) of purified embryonic rat motoneurons. Moreover, HGF/SF is an essential component of muscle-derived support for motoneurons, since blocking antibodies to HGF/SF specifically inhibited 65% of the trophic activity of media conditioned by C2/C7 skeletal myotubes, but did not inhibit the trophic activity secreted by Schwann cell lines. High levels of expression of the HGF/SF receptor c-Met in the spinal cord are restricted to subsets of motoneurons, mainly in limb-innervating segments. Consistent with this distribution, cultured motoneurons from limb-innervating brachial and lumbar segments showed a more potent response to HGF/SF than did thoracic motoneurons. By the end of the period of motoneuron cell death, levels of c-Met mRNA in motoneurons were markedly reduced, suggesting that the effects of HGF/SF may be limited to the period of motoneuron cell death. HGF/SF may play an important role during motoneuron development as a muscle-derived survival factor for a subpopulation of limb-innervating motoneurons.
Yamamoto
Y
Y
INSERM U382, Developmental Biology Institute of Marseille (CNRS-INSERM-Université de la Mediterranée), Campus de Luminy, France.
Livet
J
J
Pollock
R A
RA
Garces
A
A
Arce
V
V
deLapeyrière
O
O
Henderson
C E
CE
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005121:Extremities; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013127:Spinal Nerves / Q000196:embryology
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases