Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
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DOI：
10.1523/jneurosci.2358-11.2011
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发表时间：
2011-07-27
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影响因子：
--
通讯作者：
Goodrich LV
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文献类型：
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作者：
Lu CC;Appler JM;Houseman EA;Goodrich LV
听觉依赖于通过螺旋神经节（SG）神经元将声音信息从耳朵忠实地传递到大脑。然而，SG神经元是如何形成听觉处理基础的连接和特性的，这在很大程度上是未知的。我们对小鼠SG神经元的基因表达进行了分类，从胚胎第12天（E12）开始，即SG神经元首次延伸投射，直到出生后第15天（P15），即听力开始后。为了比较，我们还分析了与之密切相关的前庭神经节（VG）。基因本体分析证实，与基因调控和神经突生长相关的基因在早期表达丰富，SG和VG往往表达同一基因家族的不同成员。在后期阶段，神经元转录更多与成熟功能相关的基因，并表现出免疫基因表达的急剧增加。两个群体的比较表明，TGFβ通路组分在SG神经元中的表达增强，并建立了一致区分听觉和前庭神经元的新标记。出乎意料的是，我们发现通常与听觉发育相关的转录因子Gata3在早期阶段也在VG神经元中表达。因此，我们定义了在SG神经元中独特表达的转录因子和轴突引导分子的新队列，并可能驱动其分化和连接的听觉特异性方面。我们发现其中一种分子，受体鸟酰环化酶Npr2，是SG中央轴突分叉所必需的。因此，我们的数据集为揭示特定听觉回路组装事件的分子基础提供了有用的资源。
The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our data set provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events.