Multiple roles for hepatocyte growth factor in sympathetic neuron development.
We have studied the role of hepatocyte growth factor (HGF)/Met signaling in the development of sympathetic neuroblasts and neurons. Anti-HGF antibodies reduced the number of sympathetic neuroblasts that differentiated into neurons, but neither anti-HGF antibodies nor HGF affected neuroblast proliferation. Anti-HGF antibodies also reduced the survival of neuroblasts but not sympathetic neurons. HGF greatly enhanced the neurite outgrowth of NGF-dependent sympathetic neurons throughout development. These in vitro effects of anti-HGF antibodies and HGF were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase. The Met mutation also increased sympathetic neuroblast apoptosis in vivo. Because Met and HGF are expressed in sympathetic ganglia throughout development, it is possible that the multiple effects of HGF/Met signaling on sympathetic neuroblasts and neurons occur in part by an autocrine mechanism.
Maina
F
F
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Hilton
M C
MC
Andres
R
R
Wyatt
S
S
Klein
R
R
Davies
A M
AM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000166:cytology* / Q000196:embryology*
D000906:Antibodies; D009414:Nerve Growth Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met