Netrin 1 regulates ventral tangential migration of guidepost neurons in the lateral olfactory tract

Netrin 1 regulates ventral tangential migration of guidepost neurons in the lateral olfactory tract
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DOI:
10.1242/dev.02257
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发表时间:
2006-03-01
期刊:
影响因子:
4.6
通讯作者:
Hirata, T
Hirata, T
中科院分区:
生物学2区
文献类型:
--
作者:
Kawasaki, T;Ito, K;Hirata, T

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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来构建的。我们以前曾报道过一种特殊类型的皮层神经元,很多细胞,在小鼠胚胎腹切线迁移。这些神经元起源于整个新皮层的脑室区,在新皮层的表层切向迁移到腹侧方向,在外侧嗅束(LOT)的未来通路中对齐,并最终引导LOT轴突的投射。在这项研究中,我们开发了一个器官型培养系统,以调查这种细胞迁移在发育端脑的调节。我们的数据表明,新皮层包含的信号,直接很多细胞腹侧,神经节隆起排除了很多细胞排斥迁移和很多细胞被吸引到netrin 1,轴突导向因子。此外,我们证明了netrin 1及其功能性受体Dcc编码基因的突变导致LOT细胞的不适当分布和随后的LOT投射部分中断。这些结果表明netrin 1调节LOT细胞和LOT投射的迁移,可能是通过确保这些路标神经元的正确分布。
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.