Differential regulation of axonal growth and neuromuscular junction assembly by HGF/c-Met signaling.
Dev Dyn
; 241(10): 1562-74, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22911543
ABSTRACT
BACKGROUND:
During vertebrate neuromuscular junction (NMJ) development, contact between motor axons and muscle fibers is followed by pre- and post-synaptic specialization. Using Xenopus nerve-muscle cocultures, we recently showed that spinal neurons initially contacted muscle cells by means of filopodial processes, and that muscle-derived basic fibroblast growth factor induced axonal filopodia and slowed axonal advance to promote nerve-muscle interaction and NMJ establishment. In contrast, neurotrophins enhanced axonal growth but suppressed the extension of axonal filopodia and blocked NMJ formation.RESULTS:
Here we report that hepatocyte growth factor (HGF), which also supports motor neuron survival, was expressed by Xenopus muscle cells, and that forced expression of HGF in Xenopus spinal neurons inhibited the extension of axonal filopodia. Overexpression of the HGF-receptor c-Met in neurons also blocked the formation of axonal filopodia and furthermore sped up axonal growth, but a kinase-dead form of c-Met was unable to effect these changes. Importantly, treatment of nerve-muscle cocultures with recombinant HGF or the expression of HGF or active c-Met in neurons, or that of excess HGF in muscle, inhibited nerve-induced AChR clustering in muscle.CONCLUSIONS:
Our results suggest that HGF/c-Met signaling in neurons promotes axonal growth but suppresses filopodial assembly in neurons and hinders NMJ establishment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudópodes
/
Axônios
/
Transdução de Sinais
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Fator de Crescimento de Hepatócito
/
Neurônios Motores
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Junção Neuromuscular
Limite:
Animals
Idioma:
En
Revista:
Dev Dyn
Ano de publicação:
2012
Tipo de documento:
Article