Hepatocyte growth factor-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons.
J Neurosci
; 30(37): 12414-23, 2010 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-20844136
ABSTRACT
Nociceptors in peripheral ganglia display a remarkable functional heterogeneity. They can be divided into the following two major classes peptidergic and nonpeptidergic neurons. Although RUNX1 has been shown to play a pivotal role in the specification of nonpeptidergic neurons, the mechanisms driving peptidergic differentiation remain elusive. Here, we show that hepatocyte growth factor (HGF)-Met signaling acts synergistically with nerve growth factor-tyrosine kinase receptor A to promote peptidergic identity in a subset of prospective nociceptors. We provide in vivo evidence that a population of peptidergic neurons, derived from the RUNX1 lineage, require Met activity for the proper extinction of Runx1 and optimal activation of CGRP (calcitonin gene-related peptide). Moreover, we show that RUNX1 in turn represses Met expression in nonpeptidergic neurons, revealing a bidirectional cross talk between Met and RUNX1. Together, our novel findings support a model in which peptidergic versus nonpeptidergic specification depends on a balance between HGF-Met signaling and Runx1 extinction/maintenance.
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Base de dados:
MEDLINE
Assunto principal:
Nociceptores
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Transdução de Sinais
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Diferenciação Celular
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Fator de Crescimento de Hepatócito
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Proteínas Proto-Oncogênicas c-met
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Subunidade alfa 2 de Fator de Ligação ao Core
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article