Runx1 controls auditory sensory neuron diversity in mice.
Runx1 controls auditory sensory neuron diversity in mice.
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DOI：
10.1016/j.devcel.2023.01.008
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发表时间：
2023-02
影响因子：
11.8
通讯作者：
B. R. Shrestha;Lorna Wu;L. Goodrich
中科院分区：
文献类型：
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作者：
B. R. Shrestha;Lorna Wu;L. Goodrich
小鼠体内的声音刺激由三种分子和生理上不同的感觉神经元亚型（称为 Ia、Ib 和 Ic 螺旋神经节神经元 (SGN)）编码。在这里，我们发现转录因子 Runx1 控制小鼠耳蜗中的 SGN 亚型组成。Runx1 在胚胎发生晚期富含 Ib/Ic 前体。当胚胎 SGN 失去 Runx1 后，更多的 SGN 呈现出 Ia 身份，而不是 Ib 或 Ic 身份。对于与神经元功能相关的基因而言，这种转换比与连接性相关的基因更为完整。因此，Ib/Ic 位置的突触获得了 Ia 特性。 Runx1CKO小鼠的阈上 SGN 对声音的反应增强，证实了具有 Ia 样功能特性的神经元的扩张。出生后 Runx1 缺失也将 Ib/Ic SGN 重定向到 Ia 身份，表明 SGN 身份在出生后是可塑的。总而言之，这些发现表明，正常听觉刺激编码所必需的不同神经元身份是分层出现的，并且在出生后发育过程中保持可塑性。
Sound stimulus is encoded in mice by three molecularly and physiologically diverse subtypes of sensory neurons, called Ia, Ib, and Ic spiral ganglion neurons (SGNs). Here, we show that the transcription factor Runx1 controls SGN subtype composition in the murine cochlea.Runx1is enriched in Ib/Ic precursors by late embryogenesis. Upon the loss ofRunx1from embryonic SGNs, more SGNs take on Ia rather than Ib or Ic identities. This conversion was more complete for genes linked to neuronal function than to connectivity. Accordingly, synapses in the Ib/Ic location acquired Ia properties. Suprathreshold SGN responses to sound were enhanced inRunx1CKOmice, confirming the expansion of neurons with Ia-like functional properties.Runx1deletion after birth also redirected Ib/Ic SGNs toward Ia identity, indicating that SGN identities are plastic postnatally. Altogether, these findings show that diverse neuronal identities essential for normal auditory stimulus coding arise hierarchically and remain malleable during postnatal development.