Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain
Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain
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DOI：
10.1016/j.ydbio.2006.01.031
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发表时间：
2006-05-15
影响因子：
2.7
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
--
作者：
Furusho, Miki;Ono, Katsuhiko;Ikenaka, Kazuhiro
表达胆碱乙酰转移酶（ChAT）的胆碱能神经元是基底前脑中产生的主要神经元亚群。推测为胆碱能神经元起源部位的区域通过Olig 2的表达粗略划分，Olig 2是一种碱性螺旋-环-螺旋转录因子，其包括内侧神经节隆起、间隔区和前脚内/视前区。在本研究中，我们研究了Olig 2参与胆碱能分化。当E12.5时表达Olig 2的细胞通过他莫昔芬诱导的Cre介导的重组被永久修饰以表达lacZ或EGFP基因时，到E18.5时，以报告基因表达为标记的细胞广泛分布在基底前脑中，其中一些表达神经元标记物。我们发现，在几乎所有的情况下，少数细胞是双阳性的ChAT和X-gal或EGFP。此外，在Olig 2敲除小鼠基底前脑中ChAT+细胞的数量减少至60%。在敲除小鼠前脑中没有观察到凋亡增加或增殖减少的证据。本研究提供了第一个直接证据Olig 2基因参与胆碱能分化的基底前脑。(c)2006年爱思唯尔公司All rights reserved.
Cholinergic neurons, which express choline acetyltransferase (ChAT), are a major neuron subset generated in the basal forebrain. Areas presumed to be sites of origin of cholinergic neurons are roughly demarcated by expression of Olig2, a basic helix-loop-helix transcription factor, which includes the medial ganglionic eminence, septal area, and anterior entopeduncular/preoptic area. In the present study, we examined the involvement of Olig2 in cholinergic differentiation. When the Olig2-expressing cells at E12.5 were permanently modified to express the lacZ or EGFP gene by tamoxifen-induced Cre-mediated recombination, the cells marked by reporter gene expression were widely distributed in the basal forebrain by E18.5, some of which expressed neuronal markers. We showed that a small number of cells were double-positive for ChAT and X-gal or EGFP in almost all cases. In addition, the number of ChAT+ cells was reduced to 60% in the Olig2 knockout mouse basal forebrain. No evidence of elevated apoptosis or reduced proliferation was observed in the knockout mouse forebrain. The present study provides the first direct evidence for involvement of the Olig2 gene in cholinergic differentiation in the basal forebrain. (c) 2006 Elsevier Inc. All rights reserved.