Nakamura Souichiro, Senzaki Kouji, Yoshikawa Masaaki, Nishimura Mika, Inoue Ken-Ichi, Ito Yoshiaki, Ozaki Shigeru, Shiga Takashi
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
Development. 2008 May;135(9):1703-11. doi: 10.1242/dev.015248. Epub 2008 Apr 2.
Sensory neurons in the dorsal root ganglion (DRG) specifically project axons to central and peripheral targets according to their sensory modality. However, the molecular mechanisms that govern sensory neuron differentiation and the axonal projections remain unclear. The Runt-related transcription factors, Runx1 and Runx3, are expressed in DRG neuronal subpopulations, suggesting that they might regulate the cell specification and the trajectories of specific axons. Here, we show that parvalbumin-positive DRG neurons fail to differentiate from the onset in Runx3(-/-) mice. By contrast, TrkC-positive DRG neurons differentiate normally at embryonic day (E) 11.5, but disappear by E13.5 in Runx3(-/-) mice. Subsequently, TrkC-positive DRG neurons reappear but in smaller numbers than in the wild type. In Runx3(-/-) mice, central axons of the TrkC-positive DRG neurons project to the dorsal spinal cord but not to the ventral and intermediate spinal cord, whereas the peripheral axons project to skin but not to muscle. These results suggest that Runx3 controls the acquisition of distinct proprioceptive DRG neuron identities, and that TrkC-positive DRG neurons consist of two subpopulations: Runx3-dependent early-appearing proprioceptive neurons that project to the ventral and intermediate spinal cord and muscle; and Runx3-independent late-appearing cutaneous neurons that project to the dorsal spinal cord and skin. Moreover, we show that the number of TrkA-positive DRG neurons is reduced in Runx3(-/-) mice, as compared with the wild type. These results suggest that Runx3 positively regulates the expression of TrkC and TrkA in DRG neurons.
背根神经节（DRG）中的感觉神经元根据其感觉模式将轴突特异性投射到中枢和外周靶点。然而，支配感觉神经元分化和轴突投射的分子机制仍不清楚。Runt相关转录因子Runx1和Runx3在DRG神经元亚群中表达，这表明它们可能调节细胞特化和特定轴突的轨迹。在这里，我们表明小白蛋白阳性的DRG神经元在Runx3基因敲除小鼠中从一开始就无法分化。相比之下，TrkC阳性的DRG神经元在胚胎第11.5天（E11.5）时正常分化，但在Runx3基因敲除小鼠中到E13.5时消失。随后，TrkC阳性的DRG神经元重新出现，但数量比野生型少。在Runx3基因敲除小鼠中，TrkC阳性DRG神经元的中枢轴突投射到脊髓背侧，但不到达脊髓腹侧和中间部分，而外周轴突投射到皮肤但不到达肌肉。这些结果表明，Runx3控制着不同本体感觉DRG神经元身份的获得，并且TrkC阳性DRG神经元由两个亚群组成：依赖Runx3的早期出现的本体感觉神经元，投射到脊髓腹侧、中间部分和肌肉；以及不依赖Runx3的晚期出现的皮肤神经元，投射到脊髓背侧和皮肤。此外，我们表明，与野生型相比，Runx3基因敲除小鼠中TrkA阳性DRG神经元的数量减少。这些结果表明，Runx3正向调节DRG神经元中TrkC和TrkA的表达。
