（封面圖片中沙子的不同軌跡揭示了轉(zhuǎn)錄因子Nkx2-1作為開(kāi)關(guān),，可以調(diào)節(jié)細(xì)胞的命運(yùn),，以及哺乳動(dòng)物大腦發(fā)展過(guò)程中中間神經(jīng)元的最終歸宿。）
以往的研究工作表明,，小鼠皮層中間神經(jīng)元亞型的特性直接關(guān)系到其胚胎時(shí)間和空間的起源,。這種關(guān)聯(lián)反映了決定細(xì)胞命運(yùn)的發(fā)育基因表達(dá)。
在2008年9月11日《神經(jīng)元》（Neuron）雜志刊登的最新研究中,，Butt和他的同事發(fā)現(xiàn),，神經(jīng)母細(xì)胞的Nkx2-1的表達(dá)控制著神經(jīng)元的身份選擇。他們采用了損失功能的實(shí)驗(yàn),，結(jié)果表明,，轉(zhuǎn)錄因子Nkx2-1需要適當(dāng)?shù)奶囟ㄖ虚g神經(jīng)元亞型。在不同的神經(jīng)時(shí)間點(diǎn)去除這種基因會(huì)在更為成熟的年齡段觀察到亞型中的一個(gè)開(kāi)關(guān),。Butt等的研究揭示,，母細(xì)胞中Nkx2-1的胚胎的遺傳規(guī)律與成熟神經(jīng)系統(tǒng)中神經(jīng)子細(xì)胞的功能屬性之間存在因果關(guān)系。
同源轉(zhuǎn)錄因子Nkx2-1在端腦的進(jìn)化中起著關(guān)鍵的作用,，它規(guī)定內(nèi)側(cè)神經(jīng)嵴（MGE）母細(xì)胞的身份,，介導(dǎo)幾種GABA能和膽堿能神經(jīng)元的類(lèi)型。在同期發(fā)表的另一項(xiàng)研究中,，Nóbrega-Pereira和他的同事發(fā)現(xiàn),，Nkx2-1分裂后的功能是：決定中間神經(jīng)元是否遷移到紋狀體或大腦皮層。中間神經(jīng)元遷移過(guò)程中Nkx2-1的分裂后功能源于內(nèi)側(cè)神經(jīng)嵴（MGE）,。結(jié)合小鼠遺傳學(xué),、電生理及實(shí)驗(yàn)胚胎學(xué)等實(shí)驗(yàn)表明：下調(diào)分裂后細(xì)胞Nkx2-1的表達(dá)對(duì)于中間神經(jīng)元遷移至皮層非常有必要，而保持神經(jīng)元Nkx2-1的表達(dá)則需要中間遷移到紋狀體,。Nkx2-1在源于MGE的遷移過(guò)程中發(fā)揮著十分重要的作用,，它直接調(diào)控介導(dǎo)受體——Neuropilin-2的表達(dá)，Neuropilin-2可以使中間神經(jīng)元入侵到發(fā)育中的紋狀體,。
這項(xiàng)研究成果證明,，細(xì)胞命運(yùn)的決定因素Nkx2-1調(diào)節(jié)神經(jīng)細(xì)胞遷移的方式是在細(xì)胞分裂后直接轉(zhuǎn)錄調(diào)控的介導(dǎo)受體。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
