Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, NY 14642, USA.
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1566-71. doi: 10.1073/pnas.1112392109. Epub 2012 Jan 17.
In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.
在背根脊髓中，不同的中间神经元类别通过同侧和对侧轴突途径将特定的躯体感觉信息（如触摸、热和痛）从外周传递到大脑高级中枢。背侧中间神经元在同侧和对侧投射命运之间做出选择的转录机制尚不清楚。在这里，我们表明，单个转录因子（TF）BARHL2 通过选择性抑制 dI1ipsi 神经元中的主要 dI1contra 特征，来调节本体感受 dI1 中间神经元的这种选择，尽管这两种亚型都有表达。引人注目的是，Barhl2 缺失小鼠中的 dI1ipsi 神经元在中背角深部的内侧呈现出 dI1contra 细胞定居模式，最重要的是，它们向对侧投射轴突。这些异常之前是定义 dI1contra TF 的异位 dI1ipsi 表达，以及 dI1ipsi 富集 TF BARHL1 的下调。总之，这些结果阐明了 BARHL2 作为 dI1 亚型多样化的关键有丝分裂后调节因子，以及其在 dI1 遗传层次结构中的中间位置。
