Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium

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.