Extended Data Fig. 6: Examination of NRXN1α canonical splice sites and total NRXN1 isoform expression.
From: Neuronal impact of patient-specific aberrant NRXN1α splicing
a, Pearson’s correlation of NRXN1α isoform expression across control and 3’-NRXN1+/- hiPSC-neurons (n = 99 isoforms, r computed by t-statistics). b,c, Bar plot of the total read count for each NRXN1α exon along with the fraction that each NRXN1α junction is included in control hiPSC-neurons (b) and 3’-NRXN1+/- hiPSC-neurons. Red circle indicates the novel junction created by the 3’-NRXN1+/- deletion (c). d, Schematic of the experimental design to test activity induced regulation at NRXN1α canonical splice sites. e, Fold change of canonical splice site exclusion in controls (gray) and a 3’-NRXN1+/- hiPSC-neuron (red) plus KCl compared to PBS control (dotted line). f, Bar plot showing fold change of SS4 in KCl treated control and 3’-NRXN1+/- hiPSC-neurons (compared to PBS). g, Schematic of the experimental design to test developmental regulation at NRXN1α canonical splice sites. h, Fold change of canonical splice sites in control hiPSC-neurons at 2-weeks (light gray), 4-weeks (gray) and 6-weeks (dark gray) post-differentiation compared to NPCs (dotted line). i, Specific examination of developmental exclusion of SS4. Error bars are s.e. j-m, Expression of levels of all NRXN1 isoforms (j), NRXN1α (k), NRXN1β (l), NRXN1γ (m) across NRXN1 genotypes (8 control, 3 donors; 5 3’-NRXN1+/-, 2 donors; 5 5’-NRXN1+/-, 2 donors) in hiPSC-neurons. Violin plot displays density and range with P < 0.05 indicated by “*” from Wilcoxon Signed Rank Test. n, Pearson’s correlation of all NRXN1 isoforms (18 samples, 6 donors) with NRXN1α, NRXN1β and NRXN1γ (r values calculated using t-statistics).
