Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium
Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium
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DOI：
10.1093/cercor/12.2.129
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发表时间：
2002-02-01
期刊：
影响因子：
3.7
通讯作者：
Mallamaci, A
中科院分区：
文献类型：
--
作者：
Muzio, L;DiBenedetto, B;Mallamaci, A
最近已经证明，转录因子基因Emx 2和Pax 6，在发育中的大脑皮层沿沿着两个互补的切向梯度表达，是必不可少的形成的皮质区域配置文件在发育后期的年龄，当皮质神经元发生几乎完成。在这项研究中，我们解决了一个问题，是否皮质区域化已经受到影响的Emx 2和Pax 6功能丧失突变体在神经元发生的开始。通过比较这些突变体在这个年龄段的选定分子标记的表达模式，我们发现：（i）Emx 2和Pax 6是建立各自特异性表达谱所必需的，并且能够相互下调;和（ii）功能性EMX 2或PAX 6蛋白的缺失分别导致尾内侧和头外侧皮质区的减少，以及在皮层区域的中间-尾部边缘的WNT信号传导中心的损伤中，这对皮层生长至关重要。这些结果表明，前神经元皮质区域化可能依赖于这两个转录因子之间的相互作用，以及Emx 2（-/-）和Pax 6（-/-）突变体的晚期区域表型可能是由于皮质分子原图谱的错误配置和皮质生长曲线的扭曲。
It has recently been demonstrated that the transcription factor genes Emx2 and Pax6, expressed in the developing cerebral cortex along two complementary tangential gradients, are essential for the shaping of the cortical areal profile at late developmental ages, when cortical neuronogenesis is almost completed. In this study we addressed the question of whether cortical regionalization is already affected in Emx2 and Pax6 loss of function mutants at the beginning of neuronogenesis. By comparing expression patterns of selected molecular markers in these mutants at this age, we found that: (i) Emx2 and Pax6 are necessary for the establishment of their own specific expression profiles and are able to down-regulate each other; and (ii) absence of functional EMX2 or PAX6 proteins results in reduction of caudal-medial and rostral-lateral cortical regions, respectively, as well as in impairment of the WNT signalling center at the medial-caudal edge of the cortical field, crucial for cortical growth. These results suggest that pre-neuronogenic cortical regionalization may rely on mutual interactions between these two transcription factors and that the late areal phenotype of Emx2(-/-) and Pax6(-/-) mutants may possibly arise from both misconfiguration of the cortical molecular protomap and distortion of the cortical growth profile.