（封面图片中沙子的不同轨迹揭示了转录因子Nkx2-1作为开关，可以调节细胞的命运，以及哺乳动物大脑发展过程中中间神经元的最终归宿。）
以往的研究工作表明，小鼠皮层中间神经元亚型的特性直接关系到其胚胎时间和空间的起源。这种关联反映了决定细胞命运的发育基因表达。
在2008年9月11日《神经元》（Neuron）杂志刊登的最新研究中，Butt和他的同事发现，神经母细胞的Nkx2-1的表达控制着神经元的身份选择。他们采用了损失功能的实验，结果表明，转录因子Nkx2-1需要适当的特定中间神经元亚型。在不同的神经时间点去除这种基因会在更为成熟的年龄段观察到亚型中的一个开关。Butt等的研究揭示，母细胞中Nkx2-1的胚胎的遗传规律与成熟神经系统中神经子细胞的功能属性之间存在因果关系。
同源转录因子Nkx2-1在端脑的进化中起着关键的作用，它规定内侧神经嵴（MGE）母细胞的身份，介导几种GABA能和胆碱能神经元的类型。在同期发表的另一项研究中，Nóbrega-Pereira和他的同事发现，Nkx2-1分裂后的功能是：决定中间神经元是否迁移到纹状体或大脑皮层。中间神经元迁移过程中Nkx2-1的分裂后功能源于内侧神经嵴（MGE）。结合小鼠遗传学、电生理及实验胚胎学等实验表明：下调分裂后细胞Nkx2-1的表达对于中间神经元迁移至皮层非常有必要，而保持神经元Nkx2-1的表达则需要中间迁移到纹状体。Nkx2-1在源于MGE的迁移过程中发挥着十分重要的作用，它直接调控介导受体——Neuropilin-2的表达，Neuropilin-2可以使中间神经元入侵到发育中的纹状体。
这项研究成果证明，细胞命运的决定因素Nkx2-1调节神经细胞迁移的方式是在细胞分裂后直接转录调控的介导受体。（生物谷Bioon.com）
生物谷推荐原始出处：
Neuron，Vol 59, 722-732, 11 September 2008，Simon J.B. Butt, Gord Fishell
The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes
Simon J.B. Butt,1,3,4 Vitor H. Sousa,1,3 Marc V. Fuccillo,1 Jens Hjerling-Leffler,1 Goichi Miyoshi,1 Shioko Kimura,2 and Gord Fishell1,
1 Smilow Neuroscience Program and the Department of Cell Biology, New York University, New York, NY 10016, USA
2 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Summary
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.
Neuron，Vol 59, 733-745, 11 September 2008，Sandrina Nóbrega-Pereira, Oscar Marín
Postmitotic Nkx2-1 Controls the Migration of Telencephalic Interneurons by Direct Repression of Guidance Receptors
Sandrina Nóbrega-Pereira,1,2 Nicoletta Kessaris,3 Tonggong Du,4 Shioko Kimura,5 Stewart A. Anderson,4 and Oscar Marín1,
1 Instituto de Neurociencias de Alicante, CSIC & Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain
2 PhD Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
3 Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London WC1E 6AE, UK
4 Department of Psychiatry, Weill Medical College of Cornell University, 1300 York Avenue, Box 244, New York, NY 10021, USA
5 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Summary
The homeodomain transcription factor Nkx2-1 plays key roles in the developing telencephalon, where it regulates the identity of progenitor cells in the medial ganglionic eminence (MGE) and mediates the specification of several classes of GABAergic and cholinergic neurons. Here, we have investigated the postmitotic function of Nkx2-1 in the migration of interneurons originating in the MGE. Experimental manipulations and mouse genetics show that downregulation of Nkx2-1 expression in postmitotic cells is necessary for the migration of interneurons to the cortex, whereas maintenance of Nkx2-1 expression is required for interneuron migration to the striatum. Nkx2-1 exerts this role in the migration of MGE-derived interneurons by directly regulating the expression of a guidance receptor, Neuropilin-2, which enables interneurons to invade the developing striatum. Our results demonstrate a role for the cell-fate determinant Nkx2-1 in regulating neuronal migration by direct transcriptional regulation of guidance receptors in postmitotic cells.
