Calretinin is a cytoplasmic protein abundantly expressed by cortical and retinal interneurons50. At 5 weeks, the calretinin interneurons were abundant in the CZ (Fig. 4c), and less abundant in the IZ in control organoids (Fig. 4e). The density of the calretinin neurons in schizophrenia organoids appeared somewhat reduced, but this change was not significant (Supplementary Fig. 3a and b). Also, the length of calretinin neurons, including processes, was not significantly different between the control and schizophrenia organoids (Fig. 3, c1, c2). Calretinin interneurons are known to form horizontal connections between cortical neurons and cortical fields51. Consistent with this function, calretinin+ processes ran predominantly parallel or near parallel to the cortical surface of the control organoids. In contrast, in schizophrenia organoids, this preferential horizontal directionality was lost. Thus, the formation of connections between cortical fields by the calretinin interneurons was diminished in the developing schizophrenia cortex.
