Muzio Luca, Di Benedetto Barbara, Stoykova Anastassia, Boncinelli Edoardo, Gruss Peter, Mallamaci Antonello
Department of Biological and Technological Research (DIBIT), Istituto Scientifico H. San Raffaele, via Olgettina 58, 20132 Milano, Italy.
Cereb Cortex. 2002 Feb;12(2):129-39. doi: 10.1093/cercor/12.2.129.
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.
最近有研究表明，转录因子基因Emx2和Pax6在发育中的大脑皮层沿着两个互补的切线梯度表达，在发育后期皮层神经发生几乎完成时，它们对于皮层区域轮廓的形成至关重要。在本研究中，我们探讨了在神经发生开始时Emx2和Pax6功能丧失突变体中皮层区域化是否已经受到影响的问题。通过比较这些突变体在这个年龄时选定分子标记的表达模式，我们发现：（i）Emx2和Pax6对于建立它们自己特定的表达谱是必需的，并且能够相互下调；（ii）功能性EMX2或PAX6蛋白的缺失分别导致尾内侧和 Rostral外侧皮层区域的减少，以及皮层场尾内侧边缘WNT信号中心的受损，这对皮层生长至关重要。这些结果表明，神经发生前的皮层区域化可能依赖于这两种转录因子之间的相互作用，并且Emx2(-/-)和Pax6(-/-)突变体的后期区域表型可能源于皮层分子原图谱的错误配置和皮层生长轮廓的扭曲。
