Reelin Signaling by the Prime Neurogenic Niche of the Adult Brain

Background: During development, reelin sets the pace of neocortical neurogenesis, enabling newborn neurons to migrate. However, whether—and, if so, how—reelin signaling affects the adult neurogenic niches remains uncertain. Methods: In the present study, we use both loss- and gain-of-function genetic approaches, along with in vivo and ex vivo assays, to investigate this question. Results: We show that reelin signaling, resulting in Dab1 phosphorylation, occurs in the ependymal-subependymal zone (EZ/SEZ) of the lateral ventricles, where, along with its associated rostral migratory stream (RMS), the highest density of functional ApoER2 accumulates. Mice deficient in Reelin, ApoER2, or Dab1 exhibit enlarged ventricles and a dysplastic RMS. Moreover, while the conditional ablation of Dab1 in neural progenitor cells (NPCs) enlarges the ventricles and impairs neuroblast clearance from the SEZ, the transgenic misexpression of Reelin in NPCs of Reelin-deficient mice normalizes the ventricular lumen and the density of ependymal cilia, thereby ameliorating neuroblast migration. Consistently, intraventricular infusion of reelin reroutes neuroblasts. Conclusions: These results demonstrate that reelin signaling persists, sustaining the germinal niche of the lateral ventricles and influencing neuroblast migration in the adult brain.