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Accueil > Bibliographie > Hepatocyte growth factor-Met signaling is required for Runx1 extinction and (...)

Hepatocyte growth factor-Met signaling is required for (...)

J Neurosci. 2010 Sep ;30(37):12414-23
Hepatocyte growth factor-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons.
Gascon E, Gaillard S, Malapert P, Liu Y, Rodat-Despoix L, Samokhvalov IM, Delmas P, Helmbacher F, Maina F, Moqrich A.

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.

PubMed

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