Eli and Edythe Broad Institute of Regeneration Medicine and Stem Cell Research, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA.
Nature. 2011 Sep 28;478(7369):382-6. doi: 10.1038/nature10487.
The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb--we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.
许多成年非人类哺乳动物的侧脑室下区会产生大量新的神经元,这些神经元 destined for 嗅球。在侧脑室的壁上,未成熟的神经元祖细胞以切线方向迁移的链状结构迁移,这些结构合并成一个从侧脑室下区到嗅球的 rostral migratory stream (RMS)。相比之下,成年人类的侧脑室下区包含一个细胞稀少的间隙层,将室管膜 lining 与室周胶质 ribbon 分隔开来。这些侧脑室下区胶质细胞中的一些可以在体外作为神经干细胞发挥作用,但它们在体内的功能仍存在争议。最初的一项研究报告发现,成年人类 RMS 中的侧脑室下区增殖细胞和迁移的未成熟神经元很少。相比之下,随后的一项研究表明,人类侧脑室下区和 RMS 中存在强烈的增殖和迁移。在这里,我们发现,在 18 个月之前,婴儿人类侧脑室下区和 RMS 含有广泛的迁移未成熟神经元的通道,但与之前的报告相反,这种生殖活动在较大的儿童中减弱,并在成年时几乎消失。令人惊讶的是,在这个有限的神经发生窗口期间,并非所有人类侧脑室下区的新神经元都注定要迁移到嗅球——我们描述了一个在人类中针对前额叶皮层的主要迁移途径。总之,这些发现揭示了人类早期 postnatal 侧脑室下区和皮层中存在强烈的切线迁移未成熟神经元流。这些途径代表了影响新生儿的神经损伤的潜在靶标。