Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA 02114, USA; Department of Otolaryngology, Harvard Medical School, Boston, MA 02114, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Dev Cell. 2023 Feb 27;58(4):306-319.e5. doi: 10.1016/j.devcel.2023.01.008. Epub 2023 Feb 16.
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. Runx1 is enriched in Ib/Ic precursors by late embryogenesis. Upon the loss of Runx1 from 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 in Runx1 mice, confirming the expansion of neurons with Ia-like functional properties. Runx1 deletion 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.
声音刺激在小鼠中由三种分子和生理上不同的感觉神经元亚型编码，称为 Ia、Ib 和 Ic 螺旋神经节神经元 (SGN)。在这里，我们表明转录因子 Runx1 控制着小鼠耳蜗中 SGN 亚型的组成。Runx1 在胚胎后期富集在 Ib/Ic 前体中。当 Runx1 从胚胎 SGN 中丢失时，更多的 SGN 获得 Ia 而不是 Ib 或 Ic 身份。这种转换对于与神经元功能相关的基因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。在 Runx1 小鼠中，对声音的超阈值 SGN 反应增强，证实了具有 Ia 样功能特性的神经元的扩展。出生后 Runx1 的缺失也使 Ib/Ic SGN 向 Ia 身份重新定向，表明 SGN 身份在出生后具有可塑性。总而言之，这些发现表明，正常听觉刺激编码所必需的多种神经元身份是层次化的，并在出生后发育过程中保持可塑。
