Corridors of Migrating Neurons in Human Brain and Their Decline during Infancy

By N. Sanai, Thuhien Nguyen, Rebecca A. Ihrie, Z. Mirzadeh, Hui-hsin Tsai, M. Wong, N. Gupta, M. Berger, E. Huang, Jose Manuel García-Verdugo and 2 more. 2011

850 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Neurology, Pediatrics, Perinatology and Child Health

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. Hongjun Song
2. Guo-li Ming
3. J. Frisén
4. K. Spalding
5. Allison M. Bond
6. O. Bergmann
7. Fred H. Gage
8. R. Hen

In Neurology

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage

Citations in the corpus

• Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults (2018, neutral): “In two adults (sample numbers 24 and 26), we also studied the ventricular wall and found rare DCX+ cells with a migratory morphology in the ventricular–subventricular zone 19,20 , providing a positive control (Extended Data Fig.”
• Dynamics of hippocampal neurogenesis in adult humans (2013, positive): “The decrease in neuroblast numbers in the subventricular zone and their migratory path suggested that there is negligible, if any, adult olfactory bulb neurogenesis in humans (Arellano and Rakic, 2011; Sanai et al., 2011; Wang et al., 2011).”
• Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later (2015, background): “Wnt signaling is important for NSC maintenance, and Wnt inhibitors Dickkopf-1 (Dkk1) and secreted frizzled-related protein 3 (sFRP3) promote NSC quiescence (Jang et al., 2013; Seib et al., 2013).”
• The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016, neutral): “Additional neocortical interneurons (Sanai et al., 2011), dentate gyrus neurons (Eriksson et al., 1998), and striatal interneurons (Ernst et al., 2014) are generated after this age, extending postnatally in some instances.”