Mechanisms of neuronal localization in the developing brain

大脑皮层神经元形成六层结构，其位置取决于其出生日期。这一发育过程需要Reelin的存在，Reelin由皮质边缘区（MZ）中的Cajal-Retzius细胞分泌。然而，目前还不清楚从脑室区（VZ）到MZ下方的迁移是否是投射神经元分层的必要条件。先前的雪貂大脑皮层神经元移植研究表明，它们的最终层状命运，至少在某种程度上，在VZ中确定，但它是未知的“层状命运”最终如何定位细胞在一个特定的层。为了探索尚未到达MZ下方的皮质细胞的分离特性，将胚胎第（E）16天的VZ和中间区（IMZ）细胞解离，并使其在体外重新聚集1-4天。结果提示：E16时，内隐带内的迁移神经元优先分布于聚集体的中心附近， ...更多信息 比VZ中的增殖细胞更多。出生日期标记后的解离/再聚集培养表明，E16 IMZ的分离特性是E14出生的细胞的特征，这些细胞在E16时在IMZ中迁移，但它们不是迁移IMZ细胞的一般特性。这种出生日期依赖的分离机制也在Reelin信号缺陷的yotari细胞中观察到。这些发现表明，皮质神经元获得出生日期依赖的隔离机制之前，他们的胞体到达MZ。与上述投射神经元相反，γ-氨基丁酸（GABA）能中间神经元出现在端脑腹侧，并切向迁移到皮质板。虽然皮质投射神经元的“由内而外”排列已经被彻底分析，但中间神经元排列的模式还没有得到很好的理解。在本研究中，我们发现，在出生后（P）9.5天的小鼠视觉皮层，出生于胚胎（E）12.5天的GABA能神经元分布在两个高峰位置，主要是在第V层和第II/III层附近，而出生于E12.5天的非GABA能神经元仅分布在第VI层的一个峰附近。在E15.5出生的两个细胞群在层II/III中仅显示一个共同的峰分布。出生于E12.5的GABA能神经元在P30时仍有两个高峰。当分析GABA能神经元的亚型时，在E12.5出生的钙视黄蛋白阳性细胞分布在皮质中靠近II/III层的一个峰位置周围，而生长抑素-这些结果表明，中间神经元的排列根据亚型和具有相同亚型的投射神经元的排列受到不同的调节胚胎起源日少

Cerebral cortical neurons form a six-layered structure in which their position depends on their birth-date. This developmental process requires the presence of Reelin, which is secreted by Cajal-Retzius cells in the cortical marginal zone (MZ). However, it is still unclear whether the migration from the ventricular zone (VZ) to beneath the MZ is essential for the projection neurons to segregate into layers. Previous transplantation studies of ferret cerebral cortical neurons suggested that their ultimate laminar fate is, at least to some extent, determined in the VZ, but it is unknown how "laminar fate" eventually positions cell in a specific layer. To explore the segregation properties of cortical cells that have not yet arrived beneath the MZ, embryonic day (E) 16 VZ and intermediate zone (IMZ) cells were dissociated and allowed to reaggregate for 1-4 days in vitro. The result suggested that the migrating neurons in the IMZ at E16 preferentially located near the center of the aggrega … More tes more than the proliferative cells in the VZ. The birth-date-labeling followed by the dissociation/reaggregation culture suggested that the segregation properties of the E16 IMZ was characteristic of the E14-born cells, which were migrating in the IMZ at E16, but they were not general properties of migrating IMZ cells. This birth-date-dependent segregation mechanism was also observed in the Reelin-signaling-deficient yotari cells. These findings suggest that cortical neurons acquire a birth-date-dependent segregation mechanism before their somas reach the MZ. In contrast to the projection neurons described above, gamma-aminobutyric acid (GABA)ergic interneurons arise in the ventral telencephalon and migrate into the cortical plate tangentially. Although the "inside-out" alignment of projection neurons in the cortex has been thoroughly analyzed, the pattern of interneuron alignment is not well understood. In this study, we show that in the postnatal day (P) 9.5 mouse visual cortex, GABAergic neurons born on embryonic day (E) 12.5 were distributed around two peak locations, mainly around layer V and also around layer II/III, while non-GABAergic neurons born on E12.5 were distributed around only one peak in layer VI. Both cell populations born on E15.5 exhibited only one common peak distribution in layer II/III. The two peak locations of GABAergic neurons born on E12.5 still existed at P30. When the subtypes of GABAergic neurons were analyzed, calretinin-positive cells born on E12.5 were distributed in the cortex around one peak location near layer II/III, whereas somatostatin-positive E12.5 cells were distributed in the cortex around one peak location near layer V. These results suggest that the alignment of interneurons is regulated differently according to subtypes and from that of projection neurons having the same embryonic day of origin. Less