Extended Data Figure 6.

A. Representative images of SOX2 and NeuN expression in 2-month-old 03231^Control and 03231^p.Q503X organoids.

B. Total number of SOX2⁺ cells in 03231^Control and 03231^p.Q503X organoids. Dot represents an average value for all organoids from 1 differentiation. Two-tailed t-test on average values for 10 organoids from 4 differentiations. P Value =0.0112. Data shown as mean ± SD.

C. Total number of NeuN positive cells in 03231^Control and 03231^p.Q503X organoids. Two-tailed t-test on average values for 10 organoids from 4 differentiations. P Value =0.0217. Data shown as mean ± SD.

D. TBR2 expression in 2-month-old Patient^Corrected and Patient^p.Q503X organoids.

E. Total number of TBR2⁺ cells in Patient^Corrected and Patient^p.Q503X organoids. Two-tailed t-test on average values for 10 organoids from 4 differentiations. P= ns. Data shown as mean ± SD.

F. SOX2 positive area in the dorsal cortex of E18.5 mouse brains. Data from WT=27, HET=24, KO =27 ventricles from 4 brains for each genotype. One Way ANOVA between the genotypes, showing a decrease in the SOX2 positive progenitor regions in Het and KO as compared to WT mice. P<0.0001. Data shown as mean ± SD.

G. SOX2 positive area in the lateral cortex of E18.5 mouse brains. Data from WT=27, HET=24, KO =27 from 4 brains for each genotype. One Way ANOVA between the genotypes. P=ns. Data shown as mean ± SD.

H. TBR2 expression in WT, Het and KO E18.5 mouse brains.

I. TBR2 thickness in the cortical plate in in WT, Het and KO E18.5 mouse brain sections. One Way ANOVA on 8 ventricles from four animals for each genotype. P=ns. Data shown as mean ± SD.

J. Number of TBR2⁺ cells in 100 um² of the VZ area in WT, Het and KO E18.5 mouse brains. One Way ANOVA on 6 ventricles from four animals for each genotype. P=ns. Data shown as mean ± SD.

K. Organoid area over time from the Patient^Corrected and Patient^p.Q503X lines. Data from 10 independent differentiations, each representing an average of 6 organoids for each time point. Data shown as mean ± SEM.

L. Organoid perimeter over time from the Patient^Corrected and Patient^p.Q503X lines. Data from 10 independent differentiations, each representing an average of 6 organoids for each time point. Data shown as mean ± SEM.

M. Head circumference measurements represented as dots from the Patient^p.Q503X donor plotted against the WHO child growth standards.