A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.
A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.
复制标题
GATA3-MAFB转录网络指导专门用于听力的突触中突触后分化。
DOI：
10.7554/elife.01341
复制
发表时间：
2013-12-10
期刊：
影响因子：
7.7
通讯作者：
Goodrich LV
中科院分区：
文献类型：
--
作者：
Yu WM;Appler JM;Kim YH;Nishitani AM;Holt JR;Goodrich LV
通过神经回路的信息流由连接神经元亚型的突触的性质决定。神经元如何获得每个突触不同的特征仍然未知。我们发现转录因子 Mafb 驱动听觉带状突触的形成，这些突触专门用于从毛细胞到螺旋神经节神经元 (SGN) 的快速传输。 Mafb 在 SGN 中发挥作用，驱动带状突触的大突触后密度 (PSD) 特征的分化。在 Mafb 突变小鼠中，SGN 无法形成正常的 PSD，导致突触数量减少和听觉反应受损。相反，增加 Mafb 会加速突触发生。此外，Mafb 负责执行由 Gata3 转录网络精心策划的 SGN 分化程序的一个分支。值得注意的是，Mafb 的恢复挽救了 Gata3 突变体中的突触缺陷。因此，Mafb 是听觉突触发生的细胞类型特异性特征的强大调节剂，为治疗听力损失提供了新的切入点。 DOI：http://dx.doi.org/10.7554/eLife.01341.001 神经系统中不同类型的神经元通过不同类型的突触相互通信。例如，在听觉系统中，信号从耳朵发送到大脑时必须保持信号的时序，这对神经系统这部分的突触提出了特殊要求。特别是，耳朵内毛细胞之间的带状突触将声波转化为神经信号，而耳蜗螺旋神经节的神经元则将有关声音频率、强度和时间的信息传递给大脑，可以以极高的保真度传输信号。人们对突触专门用于特定功能的机制知之甚少。之前的研究表明，一种名为 Gata3 的蛋白质对于螺旋神经节中神经元和突触（包括带状突触）的发育非常重要。 Gata3 是一种转录因子，控制与听觉系统相关的多种基因的表达，包括作为其他转录因子表达的基因。于等人。使用转基因小鼠来探索当螺旋神经节神经元中缺少其中一种转录因子 Mafb 时会发生什么。结果表明，当 Mafb 缺失时，带状突触不会形成，这意味着它们无法对声音做出正常反应。于等人。还研究了 Gata3 缺失的小鼠：正常情况下，这些小鼠中不会存在 Mafb，但是当使用遗传技术强制 Mafb 基因表达时，带状突触就形成了。这些发现不仅揭示了突触专门用于快速准确传输听觉信息的分子途径，还可能带来治疗人类听力损失的新方法。 DOI：http://dx.doi.org/10.7554/eLife.01341.002
Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001 Different types of neurons in the nervous system communicate with each other through different types of synapses. In the auditory system, for example, it is essential for the timing of signals to be preserved as they are sent from the ear to the brain, and this places special demands on the synapses in this part of the nervous system. In particular, the ribbon synapses that are found between the inner hair cells of the ear, which convert sound waves into neural signals, and the neurons of the spiral ganglion in the cochlea, which carry information about the frequency, intensity and timing of sounds to the brain, can transmit signals with remarkable fidelity. Little is known about the mechanisms by which synapses become specialized for particular functions. Previous work has suggested that a protein called Gata3 is important for the development of the neurons and synapses in the spiral ganglion, including ribbon synapses. Gata3 is a transcription factor that controls the expression of a wide range of genes that are involved in the auditory systems, including genes that are expressed as other transcription factors. Yu et al. used transgenic mice to explore what happened when one of these transcription factors, Mafb, was missing from neurons in the spiral ganglion. The results showed that ribbon synapses did not form when Mafb was absent, which meant that they were unable to respond normally to sounds. Yu et al. also studied mice in which Gata3 was absent: normally Mafb would not be present in these mice, but when genetic techniques were used to force the expression of the gene for Mafb, ribbon synapses were formed. As well as revealing a molecular pathway by which synapses become specialized for rapid and accurate transmission of auditory information, these findings might lead to new approaches to treating hearing loss in humans. DOI: http://dx.doi.org/10.7554/eLife.01341.002