Origin of GABAergic neurons in the human neocortex
Origin of GABAergic neurons in the human neocortex
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DOI：
10.1038/nature00779
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发表时间：
2002-06-06
期刊：
影响因子：
64.8
通讯作者：
Rakic, P
中科院分区：
文献类型：
--
作者：
Letinic, K;Zoncu, R;Rakic, P
哺乳动物的新皮质包含两大类神经元：投射神经元和局部环路神经元(1-4)。投射神经元含有兴奋性神经递质谷氨酸，而局部环路神经元是抑制性的，含有GABA(2，4)。新皮质环路的复杂功能取决于GABA能局部环路神经元的数量和多样性(1-3个)。利用逆转录病毒标记的器官类型切片培养的人胚胎前脑，我们证明了存在两种不同的新皮质GABA能神经元谱系。其中一个谱系表达Dlx1/2和Mash1转录因子，占人类新皮质GABA能神经元的65%，起源于新皮质脑室和前脑背侧脑室下区Mash1表达的前体细胞。第二个谱系以Dlx1/2表达为特征，但不表达Mash1，形成约35%的GABA能神经元，起源于前脑腹侧的神经节突起。我们认为，前脑转录因子表达模式的改变可能是产生新皮质局部回路神经元(5-11)的物种特异性程序的基础，不同的皮质中间神经元谱系在人类大脑的遗传性和获得性疾病中可能受到不同的影响。
The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons(1-4). Projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons are inhibitory, containing GABA(2,4). The complex function of neocortical circuitry depends on the number and diversity of GABAergic (gamma-aminobutyric-acid-releasing) local circuit neurons(1-3). Using retroviral labelling in organotypic slice cultures of the embryonic human forebrain, we demonstrate the existence of two distinct lineages of neocortical GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors, represents 65% of neocortical GABAergic neurons in humans, and originates from Mash1-expressing progenitors of the neocortical ventricular and subventricular zone of the dorsal forebrain. The second lineage, characterized by the expression of Dlx1/2 but not Mash1, forms around 35% of the GABAergic neurons and originates from the ganglionic eminence of the ventral forebrain. We suggest that modifications in the expression pattern of transcription factors in the forebrain may underlie species-specific programmes for the generation of neocortical local circuit neurons(5-11) and that distinct lineages of cortical interneurons may be differentially affected in genetic and acquired diseases of the human brain.