INSERM U-583, F34091 Montpellier, France.
Neuron. 2009 Dec 24;64(6):857-70. doi: 10.1016/j.neuron.2009.12.004.
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 GFRalpha2, 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 Ret and MafA progressively promote the differentiation and diversification of LTMs.
背根神经节（DRG）中的低阈值机械感受器神经元（LTMs）对于触觉至关重要。它们在皮肤中形成高度特化的末梢，并在脊髓中显示出刻板的投射。功能定义的 LTMs 依赖神经营养因子信号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是如何产生的尚不清楚。在这里，我们表明，通过独特表达转录因子 MafA、Ret 受体及其辅助受体 GFRalpha2，可以在 DRG 产生后不久识别出特定类型的 LTMs，并发现它们的特化依赖于 Ngn2。在缺乏 Ret 的小鼠中，这些 LTMs 表现出早期分化缺陷，表现为 MafA 表达减少，而在后期，它们的中枢和外周投射受损。此外，在 MafA 突变体中，离散的 LTM 亚群表现出神经营养因子受体表达的改变。我们的研究结果提供了证据，表明涉及 Ret 和 MafA 的遗传相互作用逐渐促进了 LTMs 的分化和多样化。
