Wallén A A, Castro D S, Zetterström R H, Karlén M, Olson L, Ericson J, Perlmann T
Ludwig Institute for Cancer Research, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Mol Cell Neurosci. 2001 Dec;18(6):649-63. doi: 10.1006/mcne.2001.1057.
The orphan nuclear receptor Nurr1 is essential for development of midbrain dopamine (DA) cells. In Nurr1-deficient mice, DA precursor cells fail to migrate normally, are unable to innervate target areas, and only transiently express DA cell marker genes. In the search for Nurr1-regulated genes that might explain this developmental phenotype, we found that expression of the receptor tyrosine kinase Ret is deregulated in these cells of Nurr1-deficient embryos. In addition, our analyses establish Nurr1 as an early marker for the dorsal motor nucleus (DMN) of the vagus nerve. Interestingly, Ret expression is absent also in these cells in Nurr1-targeted mice. Neuronal innervation of vagus nerve target areas appeared normal apart from a subtle disorganization of the DMN-derived nerve fibers. In conclusion, regulation of Ret by Nurr1 in midbrain DA neurons and in the DMN has implications for both embryonal development and adult physiology in which signaling by neurotrophic factors plays important roles.
孤儿核受体Nurr1对中脑多巴胺（DA）细胞的发育至关重要。在Nurr1基因缺失的小鼠中，DA前体细胞无法正常迁移，不能支配靶区域，且仅短暂表达DA细胞标记基因。在寻找可能解释这种发育表型的Nurr1调控基因的过程中，我们发现受体酪氨酸激酶Ret在Nurr1基因缺失胚胎的这些细胞中表达失调。此外，我们的分析确定Nurr1是迷走神经背运动核（DMN）的早期标记物。有趣的是，在Nurr1靶向小鼠的这些细胞中也没有Ret表达。除了DMN衍生的神经纤维有轻微紊乱外，迷走神经靶区域的神经支配似乎正常。总之，Nurr1对中脑DA神经元和DMN中Ret的调控对胚胎发育和成年生理学均有影响，其中神经营养因子的信号传导起着重要作用。
