Low-Threshold Mechanoreceptor Subtypes Selectively Express MafA and Are Specified by Ret Signaling
Low-Threshold Mechanoreceptor Subtypes Selectively Express MafA and Are Specified by Ret Signaling
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DOI：
10.1016/j.neuron.2009.12.004
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发表时间：
2009-12-24
期刊：
影响因子：
16.2
通讯作者：
Carroll, Patrick
中科院分区：
文献类型：
--
作者：
Bourane, Steeve;Garces, Alain;Carroll, Patrick
背根神经节 (DRG) 的低阈值机械感受器神经元 (LTM) 对于触觉至关重要。它们在皮肤中形成高度专业化的终端，并在脊髓中显示出定型的投影。功能定义的 LTM 依赖于神经营养蛋白信号传导来维持其出生后的存活和功能，但这些神经元在发育过程中如何产生尚不清楚。在这里，我们表明，在 DRG 发生后不久，可以通过 MafA 转录因子、Ret 受体和辅助受体 GFR α 2 的独特表达来识别特定类型的 LTM，并发现它们的规范是 Ngn2 依赖性的。在缺乏 Ret 的小鼠中，这些 LTM 表现出早期分化缺陷，如 MafA 表达减少所揭示的那样，并且在后期，它们的中枢和外周投射受到损害。此外，在 MafA 突变体中，LTM 的一个离散子集显示神经营养因子受体表达的改变。我们的结果提供了证据，表明涉及 Pet 和 MafA 的遗传相互作用逐渐促进 LTM 的分化和多样化。
Low-threshold mechanoreceptor neurons (LTMs) of the dorsal root ganglia (DRG) are essential for touch sensation. They form highly specialized terminations in the skin and display stereotyped projections in the spinal cord. Functionally defined LTMs depend on neurotrophin signaling for their postnatal survival and functioning, but how these neurons arise during development is unknown. Here, we show that specific types of LTMs can be identified shortly after DRG genesis by unique expression of the MafA transcription factor, the Ret receptor and coreceptor GFR alpha 2, and find that their specification is Ngn2 dependent. In mice lacking Ret, these LTMs display early differentiation defects, as revealed by reduced MafA expression, and at later stages their central and peripheral projections are compromised. Moreover, in MafA mutants, a discrete subset of LTMs display altered expression of neurotrophic factor receptors. Our results provide evidence that genetic interactions involving Pet and MafA progressively promote the differentiation and diversification of LTMs.