Stoykova A, Hatano O, Gruss P, Götz M
Max-Planck Institute of Biophysical Chemistry, Department of Molecular Cell Biology, D-37077 Göttingen, Germany.
Cereb Cortex. 2003 Jun;13(6):560-71. doi: 10.1093/cercor/13.6.560.
The extracellular matrix molecule reelin is a crucial molecule in CNS development, in particular in the cerebellum and cerebral cortex. In the cerebral cortex, reelin is provided by a small number of neurons located in the marginal zone (MZ). These neurons belong to the earliest neurons generated, but little is known about the molecular mechanisms of their specification. Here we describe that reelin-positive cells are strongly increased in the developing cortex of the Pax6 mutant mice Small eye. Shortly after the onset of reelin expression, the number of reelin- and calretinin-positive cells is doubled in the cortex of Pax6 mutants and this increase is further enhanced during development. In contrast, calbindin-positive cells in the MZ do not co-express reelin and are not altered in the Pax6 mutant cortex. The split of the preplate cells was also defective in the Pax6 mutant cortex, suggesting that the amount of reelin is crucial for positioning of the cortical plate between the MZ and subplate. We further show that Pax6 mutant cortical cells isolated in vitro do not develop an increase in reelin-positive cells, while cells isolated from the entire telencephalon do. Consistent with non-cell-autonomous mechanisms contributing to the increase in reelin-positive cells in the Pax6-deficient cortex, tangential migration of diverse cell types from the ventral telencephalon into the cortex is enhanced in the Pax6 mutant mice. Taken together, these experiments further elucidate how patterning of the forebrain by the transcription factor Pax6 regulates the specification of distinct neuronal subtypes in the cortical MZ.
细胞外基质分子Reelin是中枢神经系统发育中的关键分子，尤其是在小脑和大脑皮层中。在大脑皮层中，Reelin由位于边缘区（MZ）的少数神经元提供。这些神经元属于最早产生的神经元，但对其特化的分子机制知之甚少。在此我们描述，在Pax6突变小鼠“小眼”发育中的皮层中，Reelin阳性细胞显著增加。在Reelin表达开始后不久，Pax6突变体皮层中Reelin和钙视网膜蛋白阳性细胞的数量增加了一倍，并且在发育过程中这种增加进一步增强。相比之下，MZ中的钙结合蛋白阳性细胞不共表达Reelin，并且在Pax6突变体皮层中没有改变。Pax6突变体皮层中前板细胞的分裂也存在缺陷，这表明Reelin的量对于皮层板在MZ和亚板之间的定位至关重要。我们进一步表明，体外分离的Pax6突变体皮层细胞不会出现Reelin阳性细胞增加的情况，而从整个端脑分离的细胞则会。与非细胞自主机制导致Pax6缺陷皮层中Reelin阳性细胞增加一致，在Pax6突变小鼠中，多种细胞类型从腹侧端脑向皮层的切向迁移增强。综上所述，这些实验进一步阐明了转录因子Pax6如何通过前脑模式调控皮层MZ中不同神经元亚型的特化。
