Projection neurons of the spinal cord dorsal horn which transmit pain, itch and temperature information to the brain comprise the anterolateral system (AS). A recent molecular and genetic study showed that many developing AS neurons express the transcription factor Phox2a, and provided insights into the mechanisms of their ontogeny and wiring of nociceptive neuronal circuits. Here we show that the loss of the axonal guidance and neuronal migration signal netrin1 results in impaired migration of mouse Phox2a+ AS neurons into the spinal lamina I. Furthermore, we show that in the absence of Dab1, an intracellular transducer of the neuronal migration signal reelin, the migration of spinal lamina V and lateral spinal nucleus Phox2a+ AS neurons is impaired, in line with deficits in nociception seen in mice with a loss of reelin signaling. Together, these results provide evidence that netrin1 and reelin control the development of spinal nociceptive projection neurons, suggesting a mechanistic explanation for studies that link sequence variations in human genes encoding these neurodevelopmental signals and abnormal pain sensation.

中文翻译：

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Netrin1 和 reelin 信号传导是胚胎脊髓前外侧系统神经元迁移所必需的。

将疼痛、瘙痒和温度信息传递到大脑的脊髓背角的投射神经元包括前外侧系统 (AS)。最近的一项分子和遗传学研究表明，许多发育中的 AS 神经元表达转录因子 Phox2a，并提供了对其个体发育机制和伤害性神经元回路布线的见解。在这里，我们表明轴突引导和神经元迁移信号 netrin1 的丧失导致小鼠 Phox2a+ AS 神经元迁移到脊髓层 I 受损。此外，我们表明在没有 Dab1 的情况下，神经元迁移信号 reelin 的细胞内传感器，脊髓椎板 V 和外侧脊髓核 Phox2a+ AS 神经元的迁移受损，这与在 reelin 信号丢失的小鼠中看到的伤害感受缺陷一致。一起，