The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.

The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.
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DOI:
10.1016/j.neuron.2008.07.031
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发表时间:
2008-09-11
期刊:
影响因子:
16.2
通讯作者:
Fishell, Gord
Fishell, Gord
中科院分区:
医学1区
文献类型:
--
作者:
Butt, Simon J. B.;Sousa, Vitor H.;Fuccillo, Marc V.;Hjerling-Leffler, Jens;Miyoshi, Goichi;Kimura, Shioko;Fishell, Gord

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先前的工作已经证明,小鼠皮层中间神经元亚型的特征可以直接与它们的胚胎时间和空间起源相关。胚胎起源和成熟中间神经元的特征之间的关系可能通过指导细胞命运的基因的发育表达来反映。然而,一个彻底的了解,指定亚型身份的早期遗传事件已受到阻碍的围产期致死性所造成的损失,涉及在确定皮层中间神经元的基因。在这里,我们采用了一个条件性功能丧失的方法来证明,转录因子Nkx 2 -1是需要适当的规范特定的interneuron亚型。在不同的神经源性时间点去除该基因导致在更成熟年龄观察到的神经元亚型的转换。我们的策略揭示了Nkx 2 -1在祖细胞中的胚胎遗传特异性与其在成熟神经系统中的神经元后代的功能属性之间的因果关系。
Previous work has demonstrated that the character of mouse cortical interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic origin and the character of mature interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical interneurons. Here we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific interneuron subtypes. Removal of this gene at distinct neurogenic timepoints results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.
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