NKX2-1 Is Required in the Embryonic Septum for Cholinergic System Development, Learning, and Memory.
NKX2-1 Is Required in the Embryonic Septum for Cholinergic System Development, Learning, and Memory.
复制标题
在胚胎隔膜中需要NKX2-1才能进行胆碱能系统的开发，学习和记忆。
DOI：
10.1016/j.celrep.2017.07.053
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发表时间：
2017-08-15
期刊：
影响因子：
8.8
通讯作者：
Kessaris N
中科院分区：
文献类型：
--
作者：
Magno L;Barry C;Schmidt-Hieber C;Theodotou P;Häusser M;Kessaris N
转录因子NKX 2 -1以其在皮质、纹状体和苍白球神经元亚群的特化中的作用而闻名。我们证明，通过遗传命运映射和交叉局灶性间隔缺失，NKX 2 -1是选择性地需要在胚胎隔神经上皮胆碱能隔海马投射神经元和基底前脑胆碱能神经元的大子集的发展。在缺乏NKX 2 -1的情况下，这些神经元无法发育，导致海马theta节律的改变和学习和记忆的严重缺陷。我们的研究结果表明，学习和记忆是依赖于NKX 2 -1功能在胚胎隔膜，并表明，认知缺陷，有时与致病性突变NKX 2 -1在人类可能是NKX 2 -1功能丧失的直接后果。前脑胆碱能神经元亚群起源于隔NKX 2 -1+ve祖细胞隔NKX 2 -1缺失导致前脑胆碱能神经元的广泛丧失隔NKX 2 -1条件突变小鼠学习和记忆的严重缺陷胚胎隔NKX 2 -1缺失时海马网络活性的改变NKX 2 -1是发育中前脑中高度保守的模式化基因，其中的突变可导致包括认知缺陷在内的一系列疾病。使用遗传命运作图和交叉缺失，Magno et al.证明前脑胆碱能系统发育和学习记忆需要胚胎隔NKX 2 -1。
The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of cholinergic septohippocampal projection neurons and large subsets of basal forebrain cholinergic neurons. In the absence of NKX2-1, these neurons fail to develop, causing alterations in hippocampal theta rhythms and severe deficiencies in learning and memory. Our results demonstrate that learning and memory are dependent on NKX2-1 function in the embryonic septum and suggest that cognitive deficiencies that are sometimes associated with pathogenic mutations in NKX2-1 in humans may be a direct consequence of loss of NKX2-1 function. Forebrain cholinergic neuron subsets originate from septal NKX2-1+ve progenitors Septal Nkx2-1 deletion causes widespread loss of forebrain cholinergic neurons Severe deficits in learning and memory in septal Nkx2-1 conditional mutant mice Hippocampal network activity alterations in the absence of embryonic septal NKX2-1 NKX2-1 is a highly conserved patterning gene in the developing forebrain, mutations in which can lead to a spectrum of disorders including cognitive deficiencies. Using genetic fate mapping and intersectional deletion, Magno et al. demonstrate a requirement for embryonic septal NKX2-1 in forebrain cholinergic system development and learning and memory.
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影响因子：
3.5
作者：
Buzsáki, G
通讯作者：
Buzsáki, G
DOI：
10.1038/npp.2010.104
发表时间：
2011-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
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通讯作者：
Marin, Oscar
影响因子：
3.5
作者：
Hasselmo, ME
通讯作者：
Hasselmo, ME
影响因子：
16.2
作者：
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通讯作者：
Fishell, Gord