Emx2 patterns the neocortex by regulating FGF positional signaling
Emx2 patterns the neocortex by regulating FGF positional signaling
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DOI：
10.1038/nn1093
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发表时间：
2003-08-01
影响因子：
25
通讯作者：
Grove, EA
中科院分区：
文献类型：
--
作者：
Fukuchi-Shimogori, T;Grove, EA
分子遗传学研究表明成纤维细胞生长因子8（FGF8）和转录因子Emx 2参与了新皮质区地图的形成。两者都建议指定区域位置沿着的前到后轴的皮质原基。FGF8和Emx2是否独立或协调作用，或者是否一个控制另一个，尚未确定。在这里，我们报告说，Emx2，通过调节FGF8，有一个间接的，但在区域地图的发展至关重要的作用。在活的小鼠胚胎中使用电穿孔介导的基因转移，我们发现过表达Emx 2改变了区域图，但仅当异位Emx 2与FGF 8来源重叠时。此外，我们发现FGF8水平因过量的Emx2而降低，而在缺乏Emx2的小鼠中增加。最后，表征Emx2突变体的皮质结构域移位通过用截短的FGF受体构建体螯合过量的FGF8来拯救。这些发现开始阐明了新皮质区地图的信号网络。
Molecular genetic studies implicate fibroblast growth factor 8 (FGF8), and the transcription factor Emx2, in development of the neocortical area map. Both are proposed to specify area position along the anterior-to-posterior axis of the cortical primordium. Whether FGF8 and Emx2 act independently or coordinately, or whether one controls the other, has not been determined. Here we report that Emx2, by regulating FGF8, has an indirect but vital role in area-map development. Using electroporation- mediated gene transfer in living mouse embryos, we found that overexpressing Emx2 altered the area map, but only when ectopic Emx2 overlapped the FGF8 source. Furthermore, we found that FGF8 levels were decreased by excess Emx2, and increased in mice lacking Emx2. Finally, cortical domain shifts that characterize Emx2 mutants were rescued by sequestering excess FGF8 with a truncated FGF receptor construct. These findings begin to clarify the signaling network that patterns the neocortical area map.