PDF(Pubmed)
Abstract：
The cell-adhesion molecule NEPH1 is required for maintaining the structural integrity and function of the glomerulus in the kidneys. In the nervous system of Drosophila and C. elegans, it is involved in synaptogenesis and axon branching, which are essential for establishing functional circuits. In the mammalian nervous system, the expression regulation and function of Neph1 has barely been explored. In this study, we provide a spatiotemporal characterization of Neph1 expression in mouse dorsal root ganglia (DRGs) and spinal cord. After the neurogenic phase, Neph1 is broadly expressed in the DRGs and in their putative targets at the dorsal horn of the spinal cord, comprising both GABAergic and glutamatergic neurons. Interestingly, we found that PRRXL1, a homeodomain transcription factor that is required for proper establishment of the DRG-spinal cord circuit, prevents a premature expression of Neph1 in the superficial laminae of the dorsal spinal cord at E14.5, but has no regulatory effect on the DRGs or on either structure at E16.5. By chromatin immunoprecipitation analysis of the dorsal spinal cord, we identified four PRRXL1-bound regions within the Neph1 introns, suggesting that PRRXL1 directly regulates Neph1 transcription. We also showed that Neph1 is required for branching, especially at distal neurites. Together, our work showed that Prrxl1 prevents the early expression of Neph1 in the superficial dorsal horn, suggesting that Neph1 might function as a downstream effector gene for proper assembly of the DRG-spinal nociceptive circuit.
摘要：
细胞粘附分子NEPH1是维持肾脏肾小球结构完整性和功能所必需的。在果蝇和秀丽隐杆线虫的神经系统中,它参与突触发生和轴突分支，这对于建立功能电路至关重要。在哺乳动物的神经系统中，Neph1的表达调控和功能尚未被探索。在这项研究中,我们提供了小鼠背根神经节（DRGs）和脊髓中Neph1表达的时空特征。在神经性阶段之后,Neph1在DRGs及其假定的脊髓背角靶标中广泛表达，包括GABA能和谷氨酸能神经元。有趣的是,我们发现PRRXL1是正确建立DRG-脊髓回路所需的同源结构域转录因子，在E14.5阻止Neph1在脊髓背侧浅层中的过早表达，但对DRGs或E16.5的任一结构没有调节作用。通过脊髓背侧的染色质免疫沉淀分析，我们确定了Neph1内含子内的四个PRRXL1结合区域，提示PRRXL1直接调节Neph1转录。我们还表明Neph1是分支所必需的，尤其是在远端神经突.一起,我们的工作表明，Prrxl1阻止Neph1在浅层背角的早期表达，提示Neph1可能是DRG-脊髓伤害性回路正确组装的下游效应基因。
