Kawasaki Takahiko, Ito Keisuke, Hirata Tatsumi
Division of Brain Function, National Institute of Genetics, Graduate University for Advanced Studies, SOKENDAI, Yata 1111, Mishima 411-8540, Japan.
Development. 2006 Mar;133(5):845-53. doi: 10.1242/dev.02257. Epub 2006 Jan 26.
In the developing nervous system, functional neural networks are constructed with intricate coordination of neuronal migrations and axonal projections. We have previously reported a ventral tangential migration of a special type of cortical neurons, lot cells, in the mouse embryo. These neurons originate from the ventricular zone of the entire neocortex, tangentially migrate in the surface layer of the neocortex into the ventral direction, align in the future pathway of the lateral olfactory tract (LOT) and eventually guide the projection of LOT axons. In this study, we developed an organotypic culture system to investigate the regulation of this cell migration in the developing telencephalon. Our data show that the neocortex contains the signals that direct lot cells ventrally, that the ganglionic eminence excludes lot cells by repelling the migration and that lot cells are attracted to netrin 1, an axon guidance factor. Furthermore, we demonstrate that mutations in the genes encoding netrin 1 and its functional receptor Dcc lead to inappropriate distribution of lot cells and subsequent partial disruption of LOT projection. These results suggest that netrin 1 regulates the migration of lot cells and LOT projections, possibly by ensuring the correct distribution of these guidepost neurons.
在发育中的神经系统中，功能性神经网络是通过神经元迁移和轴突投射的复杂协调构建而成的。我们之前报道过在小鼠胚胎中一种特殊类型的皮质神经元——Lot细胞的腹侧切线迁移。这些神经元起源于整个新皮质的脑室区，在新皮质的表层沿腹侧切线迁移，在外侧嗅束（LOT）的未来路径上排列，最终引导LOT轴突的投射。在本研究中，我们开发了一种器官型培养系统来研究发育中的端脑中这种细胞迁移的调控机制。我们的数据表明，新皮质含有引导Lot细胞向腹侧迁移的信号，神经节隆起通过排斥迁移来排除Lot细胞，并且Lot细胞被轴突导向因子netrin 1所吸引。此外，我们证明编码netrin 1及其功能性受体Dcc的基因突变会导致Lot细胞分布异常，并随后导致LOT投射的部分破坏。这些结果表明，netrin 1可能通过确保这些引导神经元的正确分布来调节Lot细胞的迁移和LOT投射。
