Hepatocyte Growth Factor-Met Signaling Is Required for Runx1 Extinction and Peptidergic Differentiation in Primary Nociceptive Neurons
Hepatocyte Growth Factor-Met Signaling Is Required for Runx1 Extinction and Peptidergic Differentiation in Primary Nociceptive Neurons
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DOI：
10.1523/jneurosci.3135-10.2010
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发表时间：
2010-09-15
影响因子：
5.3
通讯作者：
Moqrich, Aziz
中科院分区：
文献类型：
--
作者：
Gascon, Eduardo;Gaillard, Stephane;Moqrich, Aziz
外周神经节的伤害感受器显示出显著的功能异质性。它们可以分为以下两大类：肽能神经元和非肽能神经元。虽然RUNX 1已被证明在非肽能神经元的特化中发挥关键作用，但驱动肽能分化的机制仍然难以捉摸。在这里，我们表明，肝细胞生长因子（HGF）-甲硫氨酸信号与神经生长因子-酪氨酸激酶受体A协同作用，以促进肽能身份在一个子集的前瞻性伤害感受器。我们提供了体内证据表明，一个人口的肽能神经元，来自RUNX 1谱系，需要蛋氨酸活性的Runx 1和CGRP（降钙素基因相关肽）的最佳激活的适当灭绝。此外，我们发现，RUNX 1反过来抑制Met在非肽能神经元的表达，揭示了一个双向的串扰之间的Met和RUNX 1。总之，我们的新发现支持了一个模型，其中肽能与非肽能的规范取决于HGF-Met信号传导和Runx 1灭绝/维持之间的平衡。
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.