Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord.
Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord.
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DOI：
10.1016/j.ydbio.2012.01.021
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发表时间：
2012-04-15
影响因子：
2.7
通讯作者：
Xiang M
中科院分区：
文献类型：
--
作者：
Zou M;Li S;Klein WH;Xiang M
背根神经节（DRG）的感觉神经元必须准确地投射到其中枢靶点，以将本体感受、伤害感受和机械感受信息传递到脊髓。这些不同的感觉方式和中枢连接是如何被指定和协调的仍然不清楚。鉴于POU同源域转录因子Brn 3a/Pou 4f 1和Brn 3b/Pou 4f 2在DRG和脊髓感觉神经元中的表达，我们确定了Brn 3a和Brn 3b单突变和双突变小鼠DRG和脊髓感觉神经元以及DRG中枢投射的亚型规格。一个或两个基因的失活不会导致早期脊髓神经发生的严重异常;然而，在Brn 3a单突变和Brn 3a; Brn 3b双突变小鼠中，来自DRG的感觉传入轴突不能在脊髓中形成正常的轨迹。TrkA+传入保持在背角外部并且未能延伸到脊髓中，而TrkC+本体感受传入到腹角中的投射也受损。此外，Brn 3a突变体DRG在感觉神经元特化方面有缺陷，如在早期胚胎阶段过度产生TrkB+和TrkC+神经元以及TrkA+/TrkB+和TrkA+/TrkC+双阳性细胞所标志的。在突变体的后期阶段，TrkB+、TrkC+和小白蛋白+神经元减少，而CGRP+和c-ret+神经元显著增加。此外，Brn 3a突变体DRG显示Runx 1表达的显著下调，表明Brn 3a对DRG感觉神经元特异性的调节部分由Runx 1介导。我们的研究结果共同证明了Brn 3a在产生DRG感觉神经元多样性和调节感觉传入投射到中枢靶点中的关键作用。
The sensory neurons of the dorsal root ganglia (DRG) must project accurately to their central targets to convey proprioceptive, nociceptive and mechanoreceptive information to the spinal cord. How these different sensory modalities and central connectivities are specified and coordinated still remains unclear. Given the expression of the POU homeodomain transcription factors Brn3a/Pou4f1 and Brn3b/Pou4f2 in DRG and spinal cord sensory neurons, we determined the subtype specification of DRG and spinal cord sensory neurons as well as DRG central projections in Brn3a and Brn3b single and double mutant mice. Inactivation of either or both genes causes no gross abnormalities in early spinal cord neurogenesis; however, in Brn3a single and Brn3a;Brn3b double mutant mice, sensory afferent axons from the DRG fail to form normal trajectories in the spinal cord. The TrkA+ afferents remain outside the dorsal horn and fail to extend into the spinal cord, while the projections of TrkC+ proprioceptive afferents into the ventral horn are also impaired. Moreover, Brn3a mutant DRGs are defective in sensory neuron specification, as marked by the excessive generation of TrkB+ and TrkC+ neurons as well as TrkA+/TrkB+ and TrkA+/TrkC+ double positive cells at early embryonic stages. At later stages in the mutant, TrkB+, TrkC+ and parvalbumin+ neurons diminish while there is a significant increase of CGRP+ and c-ret+ neurons. In addition, Brn3a mutant DRGs display a dramatic down-regulation of Runx1 expression, suggesting that the regulation of DRG sensory neuron specification by Brn3a is mediated in part by Runx1. Our results together demonstrate a critical role for Brn3a in generating DRG sensory neuron diversity and regulating sensory afferent projections to the central targets.
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DOI：
10.1073/pnas.90.22.10841
发表时间：
1993-11-15
影响因子：
11.1
作者：
GERRERO, MR;MCEVILLY, RJ;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
影响因子：
2.7
作者：
Gan, L;Wang, SW;Klein, WH
通讯作者：
Klein, WH
影响因子：
2.9
作者：
González-Martínez, T;Germaná, GP;Vega, JA
通讯作者：
Vega, JA
DOI：
10.1523/jneurosci.0901-11.2011
发表时间：
2011-07-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dykes IM;Tempest L;Lee SI;Turner EE
通讯作者：
Turner EE
影响因子：
4.6
作者：
Eng, SR;Lanier, J;Turner, EE
通讯作者：
Turner, EE