Yu Wei-Ming, Appler Jessica M, Kim Ye-Hyun, Nishitani Allison M, Holt Jeffrey R, Goodrich Lisa V
Department of Neurobiology, Harvard Medical School, Boston, United States.
Elife. 2013 Dec 10;2:e01341. doi: 10.7554/eLife.01341.
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.
信息流通过神经回路是由连接神经元亚型的突触性质决定的。神经元如何获得每个突触特有的特征仍然未知。我们发现转录因子Mafb驱动听觉带状突触的形成，这种突触专门用于从毛细胞到螺旋神经节神经元（SGN）的快速传递。Mafb在SGN中起作用，驱动带状突触特有的大的突触后致密物（PSD）的分化。在Mafb突变小鼠中，SGN无法发育出正常的PSD，导致突触数量减少和听觉反应受损。相反，Mafb增加会加速突触形成。此外，Mafb负责执行由Gata3转录网络精心编排的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是听觉突触形成细胞类型特异性特征的强大调节因子，为治疗听力损失提供了一个新的切入点。DOI: http://dx.doi.org/10.7554/eLife.01341.001
