PMID- 9247333 OWN - NLM STAT- MEDLINE DCOM- 19970826 LR - 20220215 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 124 IP - 15 DP - 1997 Aug TI - Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons. PG - 2903-13 AB - 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. FAU - Yamamoto, Y AU - Yamamoto Y AD - INSERM U382, Developmental Biology Institute of Marseille (CNRS-INSERM-Universite de la Mediterranee), Campus de Luminy, France. FAU - Livet, J AU - Livet J FAU - Pollock, R A AU - Pollock RA FAU - Garces, A AU - Garces A FAU - Arce, V AU - Arce V FAU - deLapeyriere, O AU - deLapeyriere O FAU - Henderson, C E AU - Henderson CE LA - eng SI - GENBANK/D10213 SI - GENBANK/M17701 SI - GENBANK/Y00671 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Culture Media, Conditioned) RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Cell Survival MH - Cells, Cultured MH - Culture Media, Conditioned MH - Extremities MH - Hepatocyte Growth Factor/metabolism/*pharmacology MH - Molecular Sequence Data MH - Motor Neurons/cytology/*physiology MH - Muscle Fibers, Skeletal/metabolism MH - Muscle, Skeletal/*embryology/metabolism MH - Proto-Oncogene Proteins c-met MH - RNA, Messenger/analysis MH - Rats MH - Receptor Protein-Tyrosine Kinases/genetics MH - Spinal Nerves/embryology EDAT- 1997/08/01 00:00 MHDA- 1997/08/01 00:01 CRDT- 1997/08/01 00:00 PHST- 1997/08/01 00:00 [pubmed] PHST- 1997/08/01 00:01 [medline] PHST- 1997/08/01 00:00 [entrez] AID - 10.1242/dev.124.15.2903 [doi] PST - ppublish SO - Development. 1997 Aug;124(15):2903-13. doi: 10.1242/dev.124.15.2903.