Butt Simon J B, Sousa Vitor H, Fuccillo Marc V, Hjerling-Leffler Jens, Miyoshi Goichi, Kimura Shioko, Fishell Gord
Smilow Neuroscience Program and the Department of Cell Biology, New York University, New York, NY 10016, USA.
Neuron. 2008 Sep 11;59(5):722-32. doi: 10.1016/j.neuron.2008.07.031.
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 time points 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.
先前的研究表明，小鼠皮质中间神经元亚型的特征可能与其胚胎期的时空起源直接相关。胚胎起源与成熟中间神经元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得以体现。然而，由于与皮质中间神经元决定相关的基因缺失导致围产期致死，对确定亚型身份的早期遗传事件的全面理解受到了阻碍。在此，我们采用条件性功能缺失方法来证明转录因子Nkx2-1是特定中间神经元亚型正确特化所必需的。在不同的神经发生时间点去除该基因会导致在更成熟阶段观察到的神经元亚型发生转变。我们的策略揭示了祖细胞中由Nkx2-1进行的胚胎遗传特化与其成熟神经系统中神经元后代的功能属性之间的因果联系。
