Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala

The disrupted cortical lamination phenotype in reeler mice and subsequent identification of the Reelin signaling pathway have strongly informed models of cortical development. We describe here a marker-based phenotyping approach to reexamine the cytoarchitectural consequences of Reelin deficiency, using high-throughput histology and newly identified panels of highly specific molecular markers. The resulting cell-type-level cytoarchitectural analysis revealed novel features of abnormal patterning in the male reeler mouse not obvious with less specific markers or histology. The reeler cortex has been described as a rough laminar inversion, but the data presented here are not compatible with this model. The reeler cortex is disrupted in a more complex fashion, with some regions showing a mirror-image laminar phenotype. Major rostrocaudal and cell-type-specific differences in the laminar phenotype between cortical areas are detailed. These and similar findings in hippocampus and amygdala have implications for mechanisms of normal brain development and abnormalities in neurodevelopmental disorders.