title: Corridors of migrating neurons in the human brain and their decline during infancy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nader
authors.initials: N
authors.lastname: Sanai
authors.forename: Thuhien
authors.initials: T
authors.lastname: Nguyen
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Ihrie
authors.forename: Zaman
authors.initials: Z
authors.lastname: Mirzadeh
authors.forename: Hui-Hsin
authors.initials: HH
authors.lastname: Tsai
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.forename: Nalin
authors.initials: N
authors.lastname: Gupta
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Eric
authors.initials: E
authors.lastname: Huang
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000166:cytology* / Q000254:growth & development*; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009474:Neurons / Q000166:cytology*; D009833:Olfactory Pathways / Q000166:cytology