The subventricular zone (SVZ) of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb (OB)1–6. 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 SVZ to the OB. The adult human SVZ, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes7. Some of these SVZ astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report finds few SVZ proliferating cells and rare migrating immature neurons in the RMS of adult humans7. In contrast, a subsequent study indicates robust proliferation and migration in the human SVZ and RMS8,9. Here, we find that the infant human SVZ and RMS contain an extensive corridor of migrating immature neurons before 18 months of age, but, contrary to previous reports8, 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 SVZ are destined for the OB – 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 SVZ and cortex. These pathways represent potential targets of neurological injuries affecting neonates.

p63 is a master regulator of stratified epithelial development that is both necessary and sufficient for specifying this multifaceted program. We show here that Perp, a tetraspan membrane protein originally identified as an apoptosis-associated target of the p53 tumor suppressor, is the first direct target of p63 clearly involved in mediating this developmental program in vivo. During embryogenesis, Perp is expressed in an epithelial pattern, and its expression depends on p63. Perp-/- mice die postnatally, with dramatic blistering in stratified epithelia symptomatic of compromised adhesion. Perp localizes specifically to desmosomes, adhesion junctions important for tissue integrity, and numerous structural defects in desmosomes are observed in Perp-deficient skin, suggesting a role for Perp in promoting the stable assembly of desmosomal adhesive complexes. These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis.