Armentano Maria, Chou Shen-Ju, Tomassy Giulio Srubek, Leingärtner Axel, O'Leary Dennis D M, Studer Michèle
Telethon Institute of Genetics and Medicine (TIGEM), Developmental Disorders Program, Via P. Castellino 111, 80131 Naples, Italy.
Nat Neurosci. 2007 Oct;10(10):1277-86. doi: 10.1038/nn1958. Epub 2007 Sep 9.
We used cortex-specific deletion of the transcription factor gene COUP-TFI (also known as Nr2f1) in mice to demonstrate previously unknown fundamental roles for it in patterning mammalian neocortex into areas. The highest COUP-TFI expression is observed in the cortical progenitors and progeny in parietal and occipital cortex that form sensory areas, and the lowest expression was observed in frontal cortex that includes motor areas. Cortical deletion of COUP-TFI resulted in massive expansion of frontal areas, including motor, to occupy most of neocortex, paralleled by marked compression of sensory areas to caudal occipital cortex. These area patterning changes are preceded and paralleled by corresponding changes in molecular markers of area identity and altered axonal projections to maintain patterned area-specific input and output connections. We conclude that COUP-TFI is required for balancing patterning of neocortex into frontal/motor and sensory areas by acting in its expression domain to repress frontal/motor area identities and to specify sensory area identities.
我们通过在小鼠中特异性敲除转录因子基因COUP-TFI（也称为Nr2f1）的皮质，来证明其在将哺乳动物新皮质划分为不同区域方面此前未知的重要作用。在形成感觉区域的顶叶和枕叶皮质的皮质祖细胞及其后代中观察到COUP-TFI的最高表达，而在包括运动区域的额叶皮质中观察到最低表达。COUP-TFI的皮质敲除导致额叶区域（包括运动区域）大量扩展，占据了大部分新皮质，同时感觉区域明显压缩至枕叶皮质尾部。这些区域模式变化之前以及同时伴随着区域身份分子标记的相应变化，以及轴突投射的改变，以维持模式化的区域特异性输入和输出连接。我们得出结论，COUP-TFI通过在其表达域中发挥作用，抑制额叶/运动区域身份并指定感觉区域身份，从而平衡新皮质划分为额叶/运动和感觉区域的模式。
