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首页> 外文期刊>The European Journal of Neuroscience >The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1.
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The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1.

机译：胆碱能基底前脑神经元的完整性取决于Nkx2-1的表达。

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摘要

The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenance of cholinergic basal forebrain neurons in mice. Notably, prenatal deletion of Nkx2-1 in GAD67-expressing neurons leads to a nearly complete loss of cholinergic neurons and parvalbumin-containing GABAergic neurons in the basal forebrain. We also show that postnatal mutation of Nkx2-1 in choline acetyltransferase-expressing cells causes a striking reduction in their number. These degenerative changes are accompanied by partial denervation of their target structures and results in a discrete impairment of spatial memory.
机译：转录因子Nkx2-1属于同源盒编码蛋白家族，在产前大脑发育中具有重要功能。 Nkx2-1是皮质前神经元和腹侧前脑的几种神经元亚型规范所必需的。而且，该转录因子通过调节指导分子的表达而参与迁移过程。有趣的是，最近在出生后的小鼠大脑中检测到Nkx2-1表达。使用两个允许产前或产后细胞类型特异性删除Nkx2-1的转基因小鼠品系，我们表明转录因子的连续表达对于小鼠胆碱能基础前脑神经元的成熟和维持至关重要。值得注意的是，GAD67表达神经元的产前缺失Nkx2-1导致基底前脑中胆碱能神经元和含小白蛋白的GABA能神经元几乎完全丧失。我们还表明，胆碱乙酰基转移酶表达细胞中Nkx2-1的产后突变会导致其数量显着减少。这些退化性变化伴随着其目标结构的部分神经缺失，并导致空间记忆的离散损伤。

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