Aberrant trajectory of ascending dopaminergic pathway in mice lacking Nkx2.1
Aberrant trajectory of ascending dopaminergic pathway in mice lacking Nkx2.1
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DOI：
10.1016/s0014-4886(03)00030-x
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Kimura, S
中科院分区：
文献类型：
--
作者：
Kawano, H;Horie, M;Kimura, S
在胚胎脑中，转录因子Nkx2.1定位于内侧神经节隆起和下丘脑腹内侧部分。在本研究中，我们研究了中脑多巴胺（DA）神经元系统在小鼠缺乏Nkx2.1的发展。在正常小鼠中，酪氨酸羟化酶免疫反应阳性轴突从中脑DA细胞延长两侧在外侧下丘脑在胚胎12.5天（E12.5）和项目同侧纹状体E14.5。在突变的大脑，中脑DA细胞群似乎正常发展，但大多数的上行轴突被观察到穿越腹侧中线的尾侧下丘脑和项目对侧纹状体。DiI，一种荧光染料，放置在腹外侧中脑的E14.5突变小鼠，进一步揭示了大部分的DiI标记的轴突投射到对侧纹状体，而一个较小的同侧投影也被观察到。在腹内侧下丘脑的突变体，第三脑室的神经上皮缺失，和semaphorin 3A，一种可溶性的轴突排斥，这是通常位于神经上皮的免疫反应性显着降低。最近的证据表明，slit2，另一个轴突排斥扩散因子的表达，也消除了Nkx2.1缺陷小鼠的下丘脑神经上皮，观察到的异常交叉上升DA轴突可能是由于消除这些化学排斥信号的突变体下丘脑的内侧部分。(C)2003 Elsevier Science（美国）。All rights reserved.
In the embryonic brain, the transcription factor Nkx2.1 is localized in the medial ganglionic eminence and the ventromedial part of the hypothalamus. In the present study, we examined the development of mesencephalic dopamine (DA) neuron system in mice lacking Nkx2.1. In normal mice, tyrosine hydroxylase-immunoreactive axons from mesencephalic DA cells extended bilaterally in the lateral hypothalamus at embryonic day 12.5 (E12.5) and project to the ipsilateral striatum by E14.5. In the mutant brain, mesencephalic DA cell groups appeared to develop normally, but the majority of their ascending axons were observed to cross the ventral midline of the caudal hypothalamus and project to the contralateral striatum. DiI, a fluorescent dye, placed in the ventrolateral mesencephalon of E14.5 mutant mice, further revealed that majority of DiI-labeled axons projected to the contralateral striatum, while a minor ipsilateral projection was also observed. In the ventromedial hypothalamus of mutants, the neuroepithelium of third ventricle was missing, and immunoreactivity of semaphorin 3A, a soluble type of axon repellent, which was normally localized in the neuroepithelium, was remarkably reduced. Together with the recent evidence that the expression of slit2, another axon-repellent diffusible factor, is also eliminated in the hypothalamic neuroepithelium of Nkx2.1-deficient mice, the abnormal crossing of ascending DA axons observed may be attributed to the elimination of these chemorepulsive signals in the medial part of the mutant hypothalamus. (C) 2003 Elsevier Science (USA). All rights reserved.