Reelin is an extracellular matrix protein, known for its dual role in neuronal migration during brain development and in synaptic plasticity at adult stages. During the perinatal phase, Reelin expression switches from Cajal-Retzius (CR) cells, its main source before birth, to inhibitory interneurons (IN), the main source of Reelin in the adult forebrain. IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear. In this study, we used conditional knockout mice, which lack Reelin expression specifically in inhibitory INs, leading to a substantial reduction in total Reelin expression in the neocortex and dentate gyrus. Our results show that IN-specific Reelin knockout mice exhibit normal neuronal layering and normal behavior, including spatial reference memory. Although INs are the major source of Reelin within the adult stem cell niche, Reelin from INs does not contribute substantially to normal adult neurogenesis. While a closer look at the dentate gyrus revealed some unexpected alterations at the cellular level, including an increase in the number of Reelin expressing CR cells, overall our data suggest that Reelin derived from INs is less critical for cortex development and function than Reelin expressed by CR cells.
