Fig. 3

NRXN3 isoforms regulate density of dendritic spines and synapses in SCZ neurons. A SCZ neurons showed significant reduction (mean + / − SEM, Mann–Whitney U test) in mRNA expression of NRXN3 (p < 0.001) and NRXN1 (p = 0.0010). B Protein levels for NRXN3β and NRXN1 in seven SCZ and seven CON cortical neurons showed lower levels NRXN3β in SCZ (mean + / − SEM, Mann–Whitney U test, p = 0.0041) but no significant difference in NRXN1. C Annotation of NRXN3 isoforms, adapted from Ensembl. D Relative expression levels of NRXN3 isoforms—NRXN3 202 represents full gene. SCZ neurons showed significant reduction (mean + / − SEM, Mann–Whitney U test) of NRXN3 isoforms 203 (p < 0.001) and 204 (p < 0.001), but not in isoforms 202, 214, or 217. E Knockdown of NRXN3 204 in CON neurons resulted in reduction in dendritic spines (p = 0.0086) and synaptic puncta (p < 0.001) compared to scrambled control shRNA (mean + / − SD, unpaired t-test with Welch’s correction). Overexpression of NRXN3 204 in SCZ neurons resulted in increased dendritic spines (p = 0.0014) and synaptic puncta (p = 0.0364) compared to overexpression of a scrambled control (mean + / − SD, unpaired t-test with Welch’s correction). F CUX1 neurons from 7 SCZ lines treated with 10 μM clozapine in triplicates showed increased density of dendritic spines and synaptic puncta (dot plots with mean + / − SEM, p < 0.0001, unpaired t-test with Welch’s correction). G SCZ cortical neurons exposed to 10 μM clozapine for 24 h showed a significant increase (mean + / − SEM, Mann–Whitney U test) in NRXN3 203 (p < 0.0012) and 204 (p < 0.0001), but not of 214 or 217