TY - JOUR T1 - Hepatocyte Growth Factor-Met Signaling Is Required for <em>Runx1</em> Extinction and Peptidergic Differentiation in Primary Nociceptive Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 12414 LP - 12423 DO - 10.1523/JNEUROSCI.3135-10.2010 VL - 30 IS - 37 AU - Eduardo Gascon AU - Stéphane Gaillard AU - Pascale Malapert AU - Yang Liu AU - Lise Rodat-Despoix AU - Igor M. Samokhvalov AU - Patrick Delmas AU - Françoise Helmbacher AU - Flavio Maina AU - Aziz Moqrich Y1 - 2010/09/15 UR - http://www.jneurosci.org/content/30/37/12414.abstract N2 - 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. ER -