We next analyzed expression of reelin, a secreted glycosylated protein deposited by the neurons of the marginal zone and other neurons in the developing cortex. Extracellular reelin supplies essential migratory cues to the waves of the developing cortico-petal neuroblasts and immature neurons and for the formation of the cortical layers49. In 2-week control organoids, reelin was not expressed, but at 5 weeks, reelin expression was detected in cells dispersed within the CZ, including its marginal layer, as well as in the IZ (Fig. 4b). Quantitative analysis of reelin immunofluorescence intensity in organoids from three patients and three controls showed a consistent depletion (−40%, p < 0.001) of reelin in the schizophrenia cortex (Fig. 4b, Supplementary Fig. 5b). A small reelin decrease in the IZ was observed in some organoids, but did not attain statistical significance (Fig. 4b, Supplementary Fig. 5b).
