Mechanism of laminar formation of cerebral cortex and layer-specific neural circuits

以前的研究已经阐明了许多基因表达的特定层的皮质层。在这些基因中，我们选择了四个基因，i。例如，mSorLA、ROR-β、ER 81和Tbr 1，并研究了reeler小鼠大脑新皮质的表型。长期以来，人们一直认为卷轴皮层是细胞结构逆转的。我们已经证明，压实的神经元成分表达每层标记物的影响，在reeler皮层，这导致不同的皮层神经元和模糊的皮层层的混合。在reeler小鼠的脊髓背角、耳蜗背侧核和小脑新皮质中也发现了类似的异常，表明Reelin对神经元的致密化至关重要。在卷叶皮层中，表达ROR-β的神经元并不广泛分散，这表明ROR-β表达神经元的致密化是由除卷叶蛋白以外的分子调节的。在reeler嗅球中，细胞结构异常也是微妙的，因此这种层状结构的形成是由不依赖于Reelin的分子调节的。总之，我们不能确定reeler皮层的反向层状结构，如许多以前的报告反复报道的，和reeler畸形是由几个机制的有趣的结果与Reelin蛋白。

Previous studies have elucidated many genes that are expressed in specific layers of cortical layers. Among these genes we chose four genes, i. e., mSorLA, ROR-beta, ER81 and Tbr1 and studied phenotypes of cerebral neocortex of the reeler mouse. It has been long considered that the reeler cortex is cytoarchitectually reversed. We have demonstrated that compaction of neuronal components expressing each layer marker is affected in the reeler cortex, which resulted in intermingling of different cortical neurons and blurred cortical layers. The similar abnormalities were also recognized in the dorsal horn of the spinal cord, dorsal cochlear nucleus and cerebellar neocortex of the reeler mouse, suggesting Reelin is essential for compaction of neurons. In the reeler cortex, ROR-beta expressing neurons are not widely scattered, suggesting compaction of ROR-beta expressing neurons-is regulated by molecules other than Reelin protein. In the reeler olfactory bulb, the cytoarchitectural abnormality is also subtle, and therefore formation of this laminar structure is regulated by Reelin-independent molecules. In conclusion, we could not identified reversed laminar structures of the reeler cortex as repeatedly reported by many previous reports, and the reeler malformation is caused by the intriguing outcomes of several mechanisms relating to Reelin protein.