The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons
The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons
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DOI：
10.1111/j.0953-816x.2004.03415.x
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Wanaka, A
中科院分区：
文献类型：
--
作者：
Mori, T;Zhang, YX;Wanaka, A
基底前脑胆碱能神经元（BFCN）参与认知功能，例如学习和记忆，并且在几种神经退行性疾病（例如阿尔茨海默病）中受到影响。尽管其重要性，其发展的分子机制尚未完全阐明。最近的报道表明，成年大鼠的一些BFCN是LIM同源框转录因子L3/Lhx 8阳性。为了检查L3/Lhx 8在BFCN发育中的功能，我们产生了L3/Lhx 8基因破坏的小鼠。在这些小鼠中，表达胆碱能神经元标记物的细胞，如胆碱乙酰转移酶，囊泡乙酰胆碱转运蛋白和p75低亲和力神经生长因子受体，在基底前脑显着减少，而其他胆碱能神经元，包括脑干和脊髓运动神经元表达的标记物。基底前脑中胆碱能神经递质表型以外的神经递质表型似乎完好无损。根据这些结果，我们认为L3/Lhx 8在BFCN的发展和/或维持中具有关键和特定的作用。
Basal forebrain cholinergic neurons (BFCNs) are involved in cognitive functions such as learning and memory, and are affected in several neurodegenerative diseases (e.g. Alzheimer's disease). Despite their importance, the molecular mechanisms of their development are not fully elucidated. A recent report demonstrated that some BFCNs in adult rat are positive for L3/Lhx8, a LIM homeobox transcription factor. To examine the function of L3/Lhx8 in the development of BFCNs, we generated L3/Lhx8 gene-disrupted mice. In these mice, cells expressing cholinergic neuron markers, such as choline acetyltransferase, vesicular acetylcholine transporter and p75 low-affinity NGF receptor, were markedly reduced in the basal forebrain, whereas other cholinergic neurons including brain stem and spinal motor neurons expressed the markers. Neurotransmitter phenotypes other than cholinergic in the basal forebrain appeared intact. From these results, we suggested that L3/Lhx8 has a pivotal and specific role in the development and/or maintenance of BFCNs.